Mitotic G1 phase and G1/S transition (Homo sapiens)

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1. Sun P, Yoshizuka N, New L, Moser BA, Li Y, Liao R, Xie C, Chen J, Deng Q, Yamout M, Dong MQ, Frangou CG, Yates JR, Wright PE, Han J.; ''PRAK is essential for ras-induced senescence and tumor suppression.''; PubMed Europe PMC Scholia
2. Chen CR, Kang Y, Siegel PM, Massagué J.; ''E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression.''; PubMed Europe PMC Scholia
3. Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, Takagi M, Matsumoto K, Miyazono K, Gotoh Y.; ''Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways.''; PubMed Europe PMC Scholia
4. Derry JJ, Richard S, Valderrama Carvajal H, Ye X, Vasioukhin V, Cochrane AW, Chen T, Tyner AL.; ''Sik (BRK) phosphorylates Sam68 in the nucleus and negatively regulates its RNA binding ability.''; PubMed Europe PMC Scholia
5. Murphy LO, Smith S, Chen RH, Fingar DC, Blenis J.; ''Molecular interpretation of ERK signal duration by immediate early gene products.''; PubMed Europe PMC Scholia
6. Guan KL, Jenkins CW, Li Y, O'Keefe CL, Noh S, Wu X, Zariwala M, Matera AG, Xiong Y.; ''Isolation and characterization of p19INK4d, a p16-related inhibitor specific to CDK6 and CDK4.''; PubMed Europe PMC Scholia
7. Barradas M, Anderton E, Acosta JC, Li S, Banito A, Rodriguez-Niedenführ M, Maertens G, Banck M, Zhou MM, Walsh MJ, Peters G, Gil J.; ''Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS.''; PubMed Europe PMC Scholia
8. Watanabe N, Broome M, Hunter T.; ''Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle.''; PubMed Europe PMC Scholia
9. New L, Jiang Y, Han J.; ''Regulation of PRAK subcellular location by p38 MAP kinases.''; PubMed Europe PMC Scholia
10. Ferreira R, Magnaghi-Jaulin L, Robin P, Harel-Bellan A, Trouche D.; ''The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase.''; PubMed Europe PMC Scholia
11. Glover JN, Harrison SC.; ''Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA.''; PubMed Europe PMC Scholia
12. Borriello A, Caldarelli I, Bencivenga D, Cucciolla V, Oliva A, Usala E, Danise P, Ronzoni L, Perrotta S, Della Ragione F.; ''p57Kip2 is a downstream effector of BCR-ABL kinase inhibitors in chronic myelogenous leukemia cells.''; PubMed Europe PMC Scholia
13. Baek KH, Ryeom S.; ''Detection of Oncogene-Induced Senescence In Vivo.''; PubMed Europe PMC Scholia
14. Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP.; ''Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase.''; PubMed Europe PMC Scholia
15. Zacksenhaus E, Bremner R, Phillips RA, Gallie BL.; ''A bipartite nuclear localization signal in the retinoblastoma gene product and its importance for biological activity.''; PubMed Europe PMC Scholia
16. Blain SW, Montalvo E, Massagué J.; ''Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 with cyclin A-Cdk2 and cyclin D2-Cdk4.''; PubMed Europe PMC Scholia
17. Bisteau X, Paternot S, Colleoni B, Ecker K, Coulonval K, De Groote P, Declercq W, Hengst L, Roger PP.; ''CDK4 T172 phosphorylation is central in a CDK7-dependent bidirectional CDK4/CDK2 interplay mediated by p21 phosphorylation at the restriction point.''; PubMed Europe PMC Scholia
18. Cerqueira A, Martín A, Symonds CE, Odajima J, Dubus P, Barbacid M, Santamaría D.; ''Genetic characterization of the role of the Cip/Kip family of proteins as cyclin-dependent kinase inhibitors and assembly factors.''; PubMed Europe PMC Scholia
19. Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D.; ''Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein.''; PubMed Europe PMC Scholia
20. Sherr CJ, Roberts JM.; ''CDK inhibitors: positive and negative regulators of G1-phase progression.''; PubMed Europe PMC Scholia
21. Orjalo AV, Bhaumik D, Gengler BK, Scott GK, Campisi J.; ''Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network.''; PubMed Europe PMC Scholia
22. Lees JA, Saito M, Vidal M, Valentine M, Look T, Harlow E, Dyson N, Helin K.; ''The retinoblastoma protein binds to a family of E2F transcription factors.''; PubMed Europe PMC Scholia
23. Zou L, Stillman B.; ''Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase.''; PubMed Europe PMC Scholia
24. Zhang Y, Xiong Y, Yarbrough WG.; ''ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways.''; PubMed Europe PMC Scholia
25. Ikeda O, Miyasaka Y, Sekine Y, Mizushima A, Muromoto R, Nanbo A, Yoshimura A, Matsuda T.; ''STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated STAT3 activation.''; PubMed Europe PMC Scholia
26. Hsu JY, Reimann JD, Sørensen CS, Lukas J, Jackson PK.; ''E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1).''; PubMed Europe PMC Scholia
27. Wohlschlegel JA, Dwyer BT, Dhar SK, Cvetic C, Walter JC, Dutta A.; ''Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.''; PubMed Europe PMC Scholia
28. Dou QP, Zhao S, Levin AH, Wang J, Helin K, Pardee AB.; ''G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter.''; PubMed Europe PMC Scholia
29. Bockstaele L, Coulonval K, Kooken H, Paternot S, Roger PP.; ''Regulation of CDK4.''; PubMed Europe PMC Scholia
30. Agherbi H, Gaussmann-Wenger A, Verthuy C, Chasson L, Serrano M, Djabali M.; ''Polycomb mediated epigenetic silencing and replication timing at the INK4a/ARF locus during senescence.''; PubMed Europe PMC Scholia
31. Acosta JC, O'Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S, Fumagalli M, Da Costa M, Brown C, Popov N, Takatsu Y, Melamed J, d'Adda di Fagagna F, Bernard D, Hernando E, Gil J.; ''Chemokine signaling via the CXCR2 receptor reinforces senescence.''; PubMed Europe PMC Scholia
32. Chien Y, Scuoppo C, Wang X, Fang X, Balgley B, Bolden JE, Premsrirut P, Luo W, Chicas A, Lee CS, Kogan SC, Lowe SW.; ''Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity.''; PubMed Europe PMC Scholia
33. Takahashi A, Imai Y, Yamakoshi K, Kuninaka S, Ohtani N, Yoshimoto S, Hori S, Tachibana M, Anderton E, Takeuchi T, Shinkai Y, Peters G, Saya H, Hara E.; ''DNA damage signaling triggers degradation of histone methyltransferases through APC/C(Cdh1) in senescent cells.''; PubMed Europe PMC Scholia
34. Lindeman GJ, Gaubatz S, Livingston DM, Ginsberg D.; ''The subcellular localization of E2F-4 is cell-cycle dependent.''; PubMed Europe PMC Scholia
35. Senturk S, Mumcuoglu M, Gursoy-Yuzugullu O, Cingoz B, Akcali KC, Ozturk M.; ''Transforming growth factor-beta induces senescence in hepatocellular carcinoma cells and inhibits tumor growth.''; PubMed Europe PMC Scholia
36. Lukong KE, Huot ME, Richard S.; ''BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest.''; PubMed Europe PMC Scholia
37. Hansen K, Farkas T, Lukas J, Holm K, Rönnstrand L, Bartek J.; ''Phosphorylation-dependent and -independent functions of p130 cooperate to evoke a sustained G1 block.''; PubMed Europe PMC Scholia
38. Jimi E, Ikebe T, Takahashi N, Hirata M, Suda T, Koga T.; ''Interleukin-1 alpha activates an NF-kappaB-like factor in osteoclast-like cells.''; PubMed Europe PMC Scholia
39. Shen CH, Chen HY, Lin MS, Li FY, Chang CC, Kuo ML, Settleman J, Chen RH.; ''Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and promote breast carcinoma growth, migration, and invasion.''; PubMed Europe PMC Scholia
40. Rayman JB, Takahashi Y, Indjeian VB, Dannenberg JH, Catchpole S, Watson RJ, te Riele H, Dynlacht BD.; ''E2F mediates cell cycle-dependent transcriptional repression in vivo by recruitment of an HDAC1/mSin3B corepressor complex.''; PubMed Europe PMC Scholia
41. Magenta A, Fasanaro P, Romani S, Di Stefano V, Capogrossi MC, Martelli F.; ''Protein phosphatase 2A subunit PR70 interacts with pRb and mediates its dephosphorylation.''; PubMed Europe PMC Scholia
42. Bagchi S, Weinmann R, Raychaudhuri P.; ''The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F.''; PubMed Europe PMC Scholia
43. Chittenden T, Livingston DM, Kaelin WG.; ''The T/E1A-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA-binding protein.''; PubMed Europe PMC Scholia
44. Coulonval K, Bockstaele L, Paternot S, Dumont JE, Roger PP.; ''The cyclin D3-CDK4-p27kip1 holoenzyme in thyroid epithelial cells: activation by TSH, inhibition by TGFbeta, and phosphorylations of its subunits demonstrated by two-dimensional gel electrophoresis.''; PubMed Europe PMC Scholia
45. Blain SW.; ''Switching cyclin D-Cdk4 kinase activity on and off.''; PubMed Europe PMC Scholia
46. Chung M, Liu C, Yang HW, Köberlin MS, Cappell SD, Meyer T.; ''Transient Hysteresis in CDK4/6 Activity Underlies Passage of the Restriction Point in G1.''; PubMed Europe PMC Scholia
47. Ostrander JH, Daniel AR, Lofgren K, Kleer CG, Lange CA.; ''Breast tumor kinase (protein tyrosine kinase 6) regulates heregulin-induced activation of ERK5 and p38 MAP kinases in breast cancer cells.''; PubMed Europe PMC Scholia
48. Yang BS, Hauser CA, Henkel G, Colman MS, Van Beveren C, Stacey KJ, Hume DA, Maki RA, Ostrowski MC.; ''Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2.''; PubMed Europe PMC Scholia
49. Bagui TK, Mohapatra S, Haura E, Pledger WJ.; ''P27Kip1 and p21Cip1 are not required for the formation of active D cyclin-cdk4 complexes.''; PubMed Europe PMC Scholia
50. Schachter MM, Merrick KA, Larochelle S, Hirschi A, Zhang C, Shokat KM, Rubin SM, Fisher RP.; ''A Cdk7-Cdk4 T-loop phosphorylation cascade promotes G1 progression.''; PubMed Europe PMC Scholia
51. Zhu XH, Nguyen H, Halicka HD, Traganos F, Koff A.; ''Noncatalytic requirement for cyclin A-cdk2 in p27 turnover.''; PubMed Europe PMC Scholia
52. Gambus A, van Deursen F, Polychronopoulos D, Foltman M, Jones RC, Edmondson RD, Calzada A, Labib K.; ''A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome.''; PubMed Europe PMC Scholia
53. Yan Z, DeGregori J, Shohet R, Leone G, Stillman B, Nevins JR, Williams RS.; ''Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.''; PubMed Europe PMC Scholia
54. Rodier F, Coppé JP, Patil CK, Hoeijmakers WA, Muñoz DP, Raza SR, Freund A, Campeau E, Davalos AR, Campisi J.; ''Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion.''; PubMed Europe PMC Scholia
55. Yoshida K, Inoue I.; ''Regulation of Geminin and Cdt1 expression by E2F transcription factors.''; PubMed Europe PMC Scholia
56. Meng W, Swenson LL, Fitzgibbon MJ, Hayakawa K, Ter Haar E, Behrens AE, Fulghum JR, Lippke JA.; ''Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export.''; PubMed Europe PMC Scholia
57. Zhou BP, Liao Y, Xia W, Spohn B, Lee MH, Hung MC.; ''Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells.''; PubMed Europe PMC Scholia
58. Ezhevsky SA, Ho A, Becker-Hapak M, Davis PK, Dowdy SF.; ''Differential regulation of retinoblastoma tumor suppressor protein by G(1) cyclin-dependent kinase complexes in vivo.''; PubMed Europe PMC Scholia
59. Shin I, Rotty J, Wu FY, Arteaga CL.; ''Phosphorylation of p27Kip1 at Thr-157 interferes with its association with importin alpha during G1 and prevents nuclear re-entry.''; PubMed Europe PMC Scholia
60. Viglietto G, Motti ML, Bruni P, Melillo RM, D'Alessio A, Califano D, Vinci F, Chiappetta G, Tsichlis P, Bellacosa A, Fusco A, Santoro M.; ''Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer.''; PubMed Europe PMC Scholia
61. Raingeaud J, Whitmarsh AJ, Barrett T, Dérijard B, Davis RJ.; ''MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway.''; PubMed Europe PMC Scholia
62. Darbinian N, Gallia GL, Kundu M, Shcherbik N, Tretiakova A, Giordano A, Khalili K.; ''Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1.''; PubMed Europe PMC Scholia
63. Zhang P, Ostrander JH, Faivre EJ, Olsen A, Fitzsimmons D, Lange CA.; ''Regulated association of protein kinase B/Akt with breast tumor kinase.''; PubMed Europe PMC Scholia
64. Kamalati T, Jolin HE, Fry MJ, Crompton MR.; ''Expression of the BRK tyrosine kinase in mammary epithelial cells enhances the coupling of EGF signalling to PI 3-kinase and Akt, via erbB3 phosphorylation.''; PubMed Europe PMC Scholia
65. Blomberg I, Hoffmann I.; ''Ectopic expression of Cdc25A accelerates the G(1)/S transition and leads to premature activation of cyclin E- and cyclin A-dependent kinases.''; PubMed Europe PMC Scholia
66. Jiang W, McDonald D, Hope TJ, Hunter T.; ''Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication.''; PubMed Europe PMC Scholia
67. Woo MS, Sánchez I, Dynlacht BD.; ''p130 and p107 use a conserved domain to inhibit cellular cyclin-dependent kinase activity.''; PubMed Europe PMC Scholia
68. Erickson S, Sangfelt O, Heyman M, Castro J, Einhorn S, Grandér D.; ''Involvement of the Ink4 proteins p16 and p15 in T-lymphocyte senescence.''; PubMed Europe PMC Scholia
69. Pires IM, Blokland NJ, Broos AW, Poujade FA, Senra JM, Eccles SA, Span PN, Harvey AJ, Hammond EM.; ''HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion.''; PubMed Europe PMC Scholia
70. Fleming Y, Armstrong CG, Morrice N, Paterson A, Goedert M, Cohen P.; ''Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7.''; PubMed Europe PMC Scholia
71. LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, Fattaey A, Harlow E.; ''New functional activities for the p21 family of CDK inhibitors.''; PubMed Europe PMC Scholia
72. Giangrande PH, Zhu W, Rempel RE, Laakso N, Nevins JR.; ''Combinatorial gene control involving E2F and E Box family members.''; PubMed Europe PMC Scholia
73. Larrea MD, Liang J, Da Silva T, Hong F, Shao SH, Han K, Dumont D, Slingerland JM.; ''Phosphorylation of p27Kip1 regulates assembly and activation of cyclin D1-Cdk4.''; PubMed Europe PMC Scholia
74. Meyerson M, Harlow E.; ''Identification of G1 kinase activity for cdk6, a novel cyclin D partner.''; PubMed Europe PMC Scholia
75. Kang SA, Lee ST.; ''PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation.''; PubMed Europe PMC Scholia
76. Serrano M, Hannon GJ, Beach D.; ''A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.''; PubMed Europe PMC Scholia
77. Sugimoto M, Martin N, Wilks DP, Tamai K, Huot TJ, Pantoja C, Okumura K, Serrano M, Hara E.; ''Activation of cyclin D1-kinase in murine fibroblasts lacking both p21(Cip1) and p27(Kip1).''; PubMed Europe PMC Scholia
78. Wotton D, Lo RS, Lee S, Massagué J.; ''A Smad transcriptional corepressor.''; PubMed Europe PMC Scholia
79. Asano M, Wharton RP.; ''E2F mediates developmental and cell cycle regulation of ORC1 in Drosophila.''; PubMed Europe PMC Scholia
80. Parry D, Bates S, Mann DJ, Peters G.; ''Lack of cyclin D-Cdk complexes in Rb-negative cells correlates with high levels of p16INK4/MTS1 tumour suppressor gene product.''; PubMed Europe PMC Scholia
81. Jackman M, Kubota Y, den Elzen N, Hagting A, Pines J.; ''Cyclin A- and cyclin E-Cdk complexes shuttle between the nucleus and the cytoplasm.''; PubMed Europe PMC Scholia
82. Lin X, Duan X, Liang YY, Su Y, Wrighton KH, Long J, Hu M, Davis CM, Wang J, Brunicardi FC, Shi Y, Chen YG, Meng A, Feng XH.; ''PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling.''; PubMed Europe PMC Scholia
83. Ohtani K, Nevins JR.; ''Functional properties of a Drosophila homolog of the E2F1 gene.''; PubMed Europe PMC Scholia
84. To KH, Pajovic S, Gallie BL, Thériault BL.; ''Regulation of p14ARF expression by miR-24: a potential mechanism compromising the p53 response during retinoblastoma development.''; PubMed Europe PMC Scholia
85. Ray A, James MK, Larochelle S, Fisher RP, Blain SW.; ''p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent modes.''; PubMed Europe PMC Scholia
86. Lin TY, Cheng YC, Yang HC, Lin WC, Wang CC, Lai PL, Shieh SY.; ''Loss of the candidate tumor suppressor BTG3 triggers acute cellular senescence via the ERK-JMJD3-p16(INK4a) signaling axis.''; PubMed Europe PMC Scholia
87. Sadasivam S, DeCaprio JA.; ''The DREAM complex: master coordinator of cell cycle-dependent gene expression.''; PubMed Europe PMC Scholia
88. White A, Pargellis CA, Studts JM, Werneburg BG, Farmer BT.; ''Molecular basis of MAPK-activated protein kinase 2:p38 assembly.''; PubMed Europe PMC Scholia
89. Depoortere F, Van Keymeulen A, Lukas J, Costagliola S, Bartkova J, Dumont JE, Bartek J, Roger PP, Dremier S.; ''A requirement for cyclin D3-cyclin-dependent kinase (cdk)-4 assembly in the cyclic adenosine monophosphate-dependent proliferation of thyrocytes.''; PubMed Europe PMC Scholia
90. Litovchick L, Florens LA, Swanson SK, Washburn MP, DeCaprio JA.; ''DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly.''; PubMed Europe PMC Scholia
91. Kang SA, Lee ES, Yoon HY, Randazzo PA, Lee ST.; ''PTK6 inhibits down-regulation of EGF receptor through phosphorylation of ARAP1.''; PubMed Europe PMC Scholia
92. Varelas X, Sakuma R, Samavarchi-Tehrani P, Peerani R, Rao BM, Dembowy J, Yaffe MB, Zandstra PW, Wrana JL.; ''TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal.''; PubMed Europe PMC Scholia
93. Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, Kawabata M, Miyazono K, Ichijo H.; ''Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1.''; PubMed Europe PMC Scholia
94. Malumbres M, Pérez De Castro I, Hernández MI, Jiménez M, Corral T, Pellicer A.; ''Cellular response to oncogenic ras involves induction of the Cdk4 and Cdk6 inhibitor p15(INK4b).''; PubMed Europe PMC Scholia
95. Li YY, Wang L, Lu CD.; ''An E2F site in the 5'-promoter region contributes to serum-dependent up-regulation of the human proliferating cell nuclear antigen gene.''; PubMed Europe PMC Scholia
96. Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T, Akira S.; ''Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8.''; PubMed Europe PMC Scholia
97. Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMed Europe PMC Scholia
98. Stroschein SL, Wang W, Zhou S, Zhou Q, Luo K.; ''Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein.''; PubMed Europe PMC Scholia
99. Narasimha AM, Kaulich M, Shapiro GS, Choi YJ, Sicinski P, Dowdy SF.; ''Cyclin D activates the Rb tumor suppressor by mono-phosphorylation.''; PubMed Europe PMC Scholia
100. Hubscher U, Maga G, Spadari S.; ''Eukaryotic DNA polymerases.''; PubMed Europe PMC Scholia
101. Paternot S, Roger PP.; ''Combined inhibition of MEK and mammalian target of rapamycin abolishes phosphorylation of cyclin-dependent kinase 4 in glioblastoma cell lines and prevents their proliferation.''; PubMed Europe PMC Scholia
102. Duronio RJ, O'Farrell PH.; ''Developmental control of a G1-S transcriptional program in Drosophila.''; PubMed Europe PMC Scholia
103. Lukas SM, Kroe RR, Wildeson J, Peet GW, Frego L, Davidson W, Ingraham RH, Pargellis CA, Labadia ME, Werneburg BG.; ''Catalysis and function of the p38 alpha.MK2a signaling complex.''; PubMed Europe PMC Scholia
104. Weinmann AS, Bartley SM, Zhang T, Zhang MQ, Farnham PJ.; ''Use of chromatin immunoprecipitation to clone novel E2F target promoters.''; PubMed Europe PMC Scholia
105. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ.; ''The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.''; PubMed Europe PMC Scholia
106. Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, Desmet CJ, Aarden LA, Mooi WJ, Peeper DS.; ''Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network.''; PubMed Europe PMC Scholia
107. Knudsen KE, Booth D, Naderi S, Sever-Chroneos Z, Fribourg AF, Hunton IC, Feramisco JR, Wang JY, Knudsen ES.; ''RB-dependent S-phase response to DNA damage.''; PubMed Europe PMC Scholia
108. Wells JM, Illenye S, Magae J, Wu CL, Heintz NH.; ''Accumulation of E2F-4.DP-1 DNA binding complexes correlates with induction of dhfr gene expression during the G1 to S phase transition.''; PubMed Europe PMC Scholia
109. Wu CL, Kirley SD, Xiao H, Chuang Y, Chung DC, Zukerberg LR.; ''Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers.''; PubMed Europe PMC Scholia
110. Wang Z, Xie Y, Zhang L, Zhang H, An X, Wang T, Meng A.; ''Migratory localization of cyclin D2-Cdk4 complex suggests a spatial regulation of the G1-S transition.''; PubMed Europe PMC Scholia
111. Brown VD, Phillips RA, Gallie BL.; ''Cumulative effect of phosphorylation of pRB on regulation of E2F activity.''; PubMed Europe PMC Scholia
112. Kukimoto I, Igaki H, Kanda T.; ''Human CDC45 protein binds to minichromosome maintenance 7 protein and the p70 subunit of DNA polymerase alpha.''; PubMed Europe PMC Scholia
113. Haegebarth A, Heap D, Bie W, Derry JJ, Richard S, Tyner AL.; ''The nuclear tyrosine kinase BRK/Sik phosphorylates and inhibits the RNA-binding activities of the Sam68-like mammalian proteins SLM-1 and SLM-2.''; PubMed Europe PMC Scholia
114. Chakraborty G, Jain S, Kundu GC.; ''Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms.''; PubMed Europe PMC Scholia
115. McLaughlin MM, Kumar S, McDonnell PC, Van Horn S, Lee JC, Livi GP, Young PR.; ''Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase.''; PubMed Europe PMC Scholia
116. Bockstaele L, Kooken H, Libert F, Paternot S, Dumont JE, de Launoit Y, Roger PP, Coulonval K.; ''Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK "inhibitors".''; PubMed Europe PMC Scholia
117. Bailly S, Fay M, Israël N, Gougerot-Pocidalo MA.; ''The transcription factor AP-1 binds to the human interleukin 1 alpha promoter.''; PubMed Europe PMC Scholia
118. Fien K, Cho YS, Lee JK, Raychaudhuri S, Tappin I, Hurwitz J.; ''Primer utilization by DNA polymerase alpha-primase is influenced by its interaction with Mcm10p.''; PubMed Europe PMC Scholia
119. Furukawa Y, Terui Y, Sakoe K, Ohta M, Saito M.; ''The role of cellular transcription factor E2F in the regulation of cdc2 mRNA expression and cell cycle control of human hematopoietic cells.''; PubMed Europe PMC Scholia
120. Litovchick L, Sadasivam S, Florens L, Zhu X, Swanson SK, Velmurugan S, Chen R, Washburn MP, Liu XS, DeCaprio JA.; ''Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence.''; PubMed Europe PMC Scholia
121. Zhang Y, Baranovskiy AG, Tahirov TH, Pavlov YI.; ''The C-terminal domain of the DNA polymerase catalytic subunit regulates the primase and polymerase activities of the human DNA polymerase α-primase complex.''; PubMed Europe PMC Scholia
122. Adams PD, Li X, Sellers WR, Baker KB, Leng X, Harper JW, Taya Y, Kaelin WG.; ''Retinoblastoma protein contains a C-terminal motif that targets it for phosphorylation by cyclin-cdk complexes.''; PubMed Europe PMC Scholia
123. Jäkel H, Weinl C, Hengst L.; ''Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control.''; PubMed Europe PMC Scholia
124. Deacon K, Blank JL.; ''Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo.''; PubMed Europe PMC Scholia
125. Lukong KE, Richard S.; ''Breast tumor kinase BRK requires kinesin-2 subunit KAP3A in modulation of cell migration.''; PubMed Europe PMC Scholia
126. Okazaki K, Sagata N.; ''The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells.''; PubMed Europe PMC Scholia
127. Sharpless NE, Sherr CJ.; ''Forging a signature of in vivo senescence.''; PubMed Europe PMC Scholia
128. New L, Jiang Y, Zhao M, Liu K, Zhu W, Flood LJ, Kato Y, Parry GC, Han J.; ''PRAK, a novel protein kinase regulated by the p38 MAP kinase.''; PubMed Europe PMC Scholia
129. Paternot S, Bockstaele L, Bisteau X, Kooken H, Coulonval K, Roger PP.; ''Rb inactivation in cell cycle and cancer: the puzzle of highly regulated activating phosphorylation of CDK4 versus constitutively active CDK-activating kinase.''; PubMed Europe PMC Scholia
130. James MK, Ray A, Leznova D, Blain SW.; ''Differential modification of p27Kip1 controls its cyclin D-cdk4 inhibitory activity.''; PubMed Europe PMC Scholia
131. Zhu W, Giangrande PH, Nevins JR.; ''E2Fs link the control of G1/S and G2/M transcription.''; PubMed Europe PMC Scholia
132. Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, Martello G, Stinchfield MJ, Soligo S, Morsut L, Inui M, Moro S, Modena N, Argenton F, Newfeld SJ, Piccolo S.; ''FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination.''; PubMed Europe PMC Scholia
133. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
134. Lee S, Shuman JD, Guszczynski T, Sakchaisri K, Sebastian T, Copeland TD, Miller M, Cohen MS, Taunton J, Smart RC, Xiao Z, Yu LR, Veenstra TD, Johnson PF.; ''RSK-mediated phosphorylation in the C/EBP{beta} leucine zipper regulates DNA binding, dimerization, and growth arrest activity.''; PubMed Europe PMC Scholia
135. Ainbinder E, Bergelson S, Pinkus R, Daniel V.; ''Regulatory mechanisms involved in activator-protein-1 (AP-1)-mediated activation of glutathione-S-transferase gene expression by chemical agents.''; PubMed Europe PMC Scholia
136. Li X, Lu Y, Liang K, Hsu JM, Albarracin C, Mills GB, Hung MC, Fan Z.; ''Brk/PTK6 sustains activated EGFR signaling through inhibiting EGFR degradation and transactivating EGFR.''; PubMed Europe PMC Scholia
137. Xiang B, Chatti K, Qiu H, Lakshmi B, Krasnitz A, Hicks J, Yu M, Miller WT, Muthuswamy SK.; ''Brk is coamplified with ErbB2 to promote proliferation in breast cancer.''; PubMed Europe PMC Scholia
138. Kamalati T, Jolin HE, Mitchell PJ, Barker KT, Jackson LE, Dean CJ, Page MJ, Gusterson BA, Crompton MR.; ''Brk, a breast tumor-derived non-receptor protein-tyrosine kinase, sensitizes mammary epithelial cells to epidermal growth factor.''; PubMed Europe PMC Scholia
139. Fuchs SY, Adler V, Buschmann T, Wu X, Ronai Z.; ''Mdm2 association with p53 targets its ubiquitination.''; PubMed Europe PMC Scholia
140. Quelle DE, Zindy F, Ashmun RA, Sherr CJ.; ''Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest.''; PubMed Europe PMC Scholia
141. Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR.; ''Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7.''; PubMed Europe PMC Scholia
142. Mizukami Y, Yoshioka K, Morimoto S, Yoshida Ki.; ''A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion.''; PubMed Europe PMC Scholia
143. Foulds CE, Nelson ML, Blaszczak AG, Graves BJ.; ''Ras/mitogen-activated protein kinase signaling activates Ets-1 and Ets-2 by CBP/p300 recruitment.''; PubMed Europe PMC Scholia
144. Saha P, Thome KC, Yamaguchi R, Hou Z, Weremowicz S, Dutta A.; ''The human homolog of Saccharomyces cerevisiae CDC45.''; PubMed Europe PMC Scholia
145. Matsushime H, Ewen ME, Strom DK, Kato JY, Hanks SK, Roussel MF, Sherr CJ.; ''Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins.''; PubMed Europe PMC Scholia
146. Peng M, Ball-Kell SM, Tyner AL.; ''Protein tyrosine kinase 6 promotes ERBB2-induced mammary gland tumorigenesis in the mouse.''; PubMed Europe PMC Scholia
147. Ohtani K, Tsujimoto A, Ikeda M, Nakamura M.; ''Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F.''; PubMed Europe PMC Scholia
148. Nicke B, Bastien J, Khanna SJ, Warne PH, Cowling V, Cook SJ, Peters G, Delpuech O, Schulze A, Berns K, Mullenders J, Beijersbergen RL, Bernards R, Ganesan TS, Downward J, Hancock DC.; ''Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth arrest in human ovarian surface epithelial cells.''; PubMed Europe PMC Scholia
149. Hukkelhoven E, Liu Y, Yeh N, Ciznadija D, Blain SW, Koff A.; ''Tyrosine phosphorylation of the p21 cyclin-dependent kinase inhibitor facilitates the development of proneural glioma.''; PubMed Europe PMC Scholia
150. Zhang H.; ''Life without kinase: cyclin E promotes DNA replication licensing and beyond.''; PubMed Europe PMC Scholia
151. Wu X, Bayle JH, Olson D, Levine AJ.; ''The p53-mdm-2 autoregulatory feedback loop.''; PubMed Europe PMC Scholia
152. Liu N, Lucibello FC, Engeland K, Müller R.; ''A new model of cell cycle-regulated transcription: repression of the cyclin A promoter by CDF-1 and anti-repression by E2F.''; PubMed Europe PMC Scholia
153. Jayadeva G, Kurimchak A, Garriga J, Sotillo E, Davis AJ, Haines DS, Mumby M, Graña X.; ''B55alpha PP2A holoenzymes modulate the phosphorylation status of the retinoblastoma-related protein p107 and its activation.''; PubMed Europe PMC Scholia
154. Kato JY, Matsuoka M, Strom DK, Sherr CJ.; ''Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase.''; PubMed Europe PMC Scholia
155. Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, Athineos D, Kang TW, Lasitschka F, Andrulis M, Pascual G, Morris KJ, Khan S, Jin H, Dharmalingam G, Snijders AP, Carroll T, Capper D, Pritchard C, Inman GJ, Longerich T, Sansom OJ, Benitah SA, Zender L, Gil J.; ''A complex secretory program orchestrated by the inflammasome controls paracrine senescence.''; PubMed Europe PMC Scholia
156. Regan Anderson TM, Peacock DL, Daniel AR, Hubbard GK, Lofgren KA, Girard BJ, Schörg A, Hoogewijs D, Wenger RH, Seagroves TN, Lange CA.; ''Breast tumor kinase (Brk/PTK6) is a mediator of hypoxia-associated breast cancer progression.''; PubMed Europe PMC Scholia
157. Ohtani K, DeGregori J, Nevins JR.; ''Regulation of the cyclin E gene by transcription factor E2F1.''; PubMed Europe PMC Scholia
158. Sanidas I, Morris R, Fella KA, Rumde PH, Boukhali M, Tai EC, Ting DT, Lawrence MS, Haas W, Dyson NJ.; ''A Code of Mono-phosphorylation Modulates the Function of RB.''; PubMed Europe PMC Scholia
159. Bell SP, Dutta A.; ''DNA replication in eukaryotic cells.''; PubMed Europe PMC Scholia
160. Seidel JJ, Graves BJ.; ''An ERK2 docking site in the Pointed domain distinguishes a subset of ETS transcription factors.''; PubMed Europe PMC Scholia
161. Hannon GJ, Beach D.; ''p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest.''; PubMed Europe PMC Scholia
162. Avni D, Yang H, Martelli F, Hofmann F, ElShamy WM, Ganesan S, Scully R, Livingston DM.; ''Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage.''; PubMed Europe PMC Scholia
163. Nakajima T, Kinoshita S, Sasagawa T, Sasaki K, Naruto M, Kishimoto T, Akira S.; ''Phosphorylation at threonine-235 by a ras-dependent mitogen-activated protein kinase cascade is essential for transcription factor NF-IL6.''; PubMed Europe PMC Scholia
164. Arata Y, Fujita M, Ohtani K, Kijima S, Kato JY.; ''Cdk2-dependent and -independent pathways in E2F-mediated S phase induction.''; PubMed Europe PMC Scholia
165. Dhar SK, Delmolino L, Dutta A.; ''Architecture of the human origin recognition complex.''; PubMed Europe PMC Scholia
166. Kumagai H, Sato N, Yamada M, Mahony D, Seghezzi W, Lees E, Arai K, Masai H.; ''A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells.''; PubMed Europe PMC Scholia
167. Masai H, Matsui E, You Z, Ishimi Y, Tamai K, Arai K.; ''Human Cdc7-related kinase complex. In vitro phosphorylation of MCM by concerted actions of Cdks and Cdc7 and that of a criticial threonine residue of Cdc7 bY Cdks.''; PubMed Europe PMC Scholia
168. Tsvetkov LM, Yeh KH, Lee SJ, Sun H, Zhang H.; ''p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27.''; PubMed Europe PMC Scholia
169. Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM.; ''Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53.''; PubMed Europe PMC Scholia
170. Fan G, Aleem S, Yang M, Miller WT, Tonks NK.; ''Protein-tyrosine Phosphatase and Kinase Specificity in Regulation of SRC and Breast Tumor Kinase.''; PubMed Europe PMC Scholia
171. Vashee S, Simancek P, Challberg MD, Kelly TJ.; ''Assembly of the human origin recognition complex.''; PubMed Europe PMC Scholia
172. Nelson ML, Kang HS, Lee GM, Blaszczak AG, Lau DK, McIntosh LP, Graves BJ.; ''Ras signaling requires dynamic properties of Ets1 for phosphorylation-enhanced binding to coactivator CBP.''; PubMed Europe PMC Scholia
173. Desai D, Wessling HC, Fisher RP, Morgan DO.; ''Effects of phosphorylation by CAK on cyclin binding by CDC2 and CDK2.''; PubMed Europe PMC Scholia
174. Matsuura H, Nishitoh H, Takeda K, Matsuzawa A, Amagasa T, Ito M, Yoshioka K, Ichijo H.; ''Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade.''; PubMed Europe PMC Scholia
175. Guan KL, Jenkins CW, Li Y, Nichols MA, Wu X, O'Keefe CL, Matera AG, Xiong Y.; ''Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function.''; PubMed Europe PMC Scholia
176. Connell-Crowley L, Harper JW, Goodrich DW.; ''Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation.''; PubMed Europe PMC Scholia
177. Li Y, Asahara H, Patel VS, Zhou S, Linn S.; ''Purification, cDNA cloning, and gene mapping of the small subunit of human DNA polymerase epsilon.''; PubMed Europe PMC Scholia
178. Wang W, Nacusi L, Sheaff RJ, Liu X.; ''Ubiquitination of p21Cip1/WAF1 by SCFSkp2: substrate requirement and ubiquitination site selection.''; PubMed Europe PMC Scholia
179. Harbour JW, Luo RX, Dei Santi A, Postigo AA, Dean DC.; ''Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1.''; PubMed Europe PMC Scholia
180. Liu S, Bolger JK, Kirkland LO, Premnath PN, McInnes C.; ''Structural and functional analysis of cyclin D1 reveals p27 and substrate inhibitor binding requirements.''; PubMed Europe PMC Scholia
181. Parisi T, Pollice A, Di Cristofano A, Calabrò V, La Mantia G.; ''Transcriptional regulation of the human tumor suppressor p14(ARF) by E2F1, E2F2, E2F3, and Sp1-like factors.''; PubMed Europe PMC Scholia
182. Hartupee J, Li X, Hamilton T.; ''Interleukin 1alpha-induced NFkappaB activation and chemokine mRNA stabilization diverge at IRAK1.''; PubMed Europe PMC Scholia
183. Atwood AA, Sealy LJ.; ''C/EBPβ's role in determining Ras-induced senescence or transformation.''; PubMed Europe PMC Scholia
184. Patel P, Asbach B, Shteyn E, Gomez C, Coltoff A, Bhuyan S, Tyner AL, Wagner R, Blain SW.; ''Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4.''; PubMed Europe PMC Scholia
185. Coppé JP, Patil CK, Rodier F, Sun Y, Muñoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J.; ''Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor.''; PubMed Europe PMC Scholia
186. Ishida N, Kitagawa M, Hatakeyama S, Nakayama K.; ''Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability.''; PubMed Europe PMC Scholia
187. Kato JY, Matsuoka M, Polyak K, Massagué J, Sherr CJ.; ''Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation.''; PubMed Europe PMC Scholia
188. Carrano AC, Eytan E, Hershko A, Pagano M.; ''SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.''; PubMed Europe PMC Scholia
189. Grimmler M, Wang Y, Mund T, Cilensek Z, Keidel EM, Waddell MB, Jäkel H, Kullmann M, Kriwacki RW, Hengst L.; ''Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases.''; PubMed Europe PMC Scholia
190. Beijersbergen RL, Carlée L, Kerkhoven RM, Bernards R.; ''Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes.''; PubMed Europe PMC Scholia
191. Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon KY, Hurwitz J, Yatagai F, Hanaoka F.; ''The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase.''; PubMed Europe PMC Scholia
192. Voncken JW, Niessen H, Neufeld B, Rennefahrt U, Dahlmans V, Kubben N, Holzer B, Ludwig S, Rapp UR.; ''MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1.''; PubMed Europe PMC Scholia
193. Sithanandam G, Latif F, Duh FM, Bernal R, Smola U, Li H, Kuzmin I, Wixler V, Geil L, Shrestha S.; ''3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region.''; PubMed Europe PMC Scholia
194. Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Mönch K, Minucci S, Porse BT, Marine JC, Hansen KH, Helin K.; ''The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells.''; PubMed Europe PMC Scholia
195. Young AR, Narita M.; ''SASP reflects senescence.''; PubMed Europe PMC Scholia
196. Bockstaele L, Bisteau X, Paternot S, Roger PP.; ''Differential regulation of cyclin-dependent kinase 4 (CDK4) and CDK6, evidence that CDK4 might not be activated by CDK7, and design of a CDK6 activating mutation.''; PubMed Europe PMC Scholia
197. Moiseeva O, Bourdeau V, Roux A, Deschênes-Simard X, Ferbeyre G.; ''Mitochondrial dysfunction contributes to oncogene-induced senescence.''; PubMed Europe PMC Scholia
198. Le Gallic L, Virgilio L, Cohen P, Biteau B, Mavrothalassitis G.; ''ERF nuclear shuttling, a continuous monitor of Erk activity that links it to cell cycle progression.''; PubMed Europe PMC Scholia
199. Chattopadhyay S, Bielinsky AK.; ''Human Mcm10 regulates the catalytic subunit of DNA polymerase-alpha and prevents DNA damage during replication.''; PubMed Europe PMC Scholia
200. Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, Parisi F, Kluger Y, Reinberg D.; ''PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes.''; PubMed Europe PMC Scholia
201. Ou L, Ferreira AM, Otieno S, Xiao L, Bashford D, Kriwacki RW.; ''Incomplete folding upon binding mediates Cdk4/cyclin D complex activation by tyrosine phosphorylation of inhibitor p27 protein.''; PubMed Europe PMC Scholia
202. Tanizaki J, Okamoto I, Sakai K, Nakagawa K.; ''Differential roles of trans-phosphorylated EGFR, HER2, HER3, and RET as heterodimerisation partners of MET in lung cancer with MET amplification.''; PubMed Europe PMC Scholia
203. Chellappan SP, Hiebert S, Mudryj M, Horowitz JM, Nevins JR.; ''The E2F transcription factor is a cellular target for the RB protein.''; PubMed Europe PMC Scholia
204. Kelly BL, Wolfe KG, Roberts JM.; ''Identification of a substrate-targeting domain in cyclin E necessary for phosphorylation of the retinoblastoma protein.''; PubMed Europe PMC Scholia
205. Niehof M, Streetz K, Rakemann T, Bischoff SC, Manns MP, Horn F, Trautwein C.; ''Interleukin-6-induced tethering of STAT3 to the LAP/C/EBPbeta promoter suggests a new mechanism of transcriptional regulation by STAT3.''; PubMed Europe PMC Scholia
206. Lukong KE, Larocque D, Tyner AL, Richard S.; ''Tyrosine phosphorylation of sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression.''; PubMed Europe PMC Scholia
207. Cheng M, Sexl V, Sherr CJ, Roussel MF.; ''Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1).''; PubMed Europe PMC Scholia
208. Atwood AA, Sealy L.; ''Regulation of C/EBPbeta1 by Ras in mammary epithelial cells and the role of C/EBPbeta1 in oncogene-induced senescence.''; PubMed Europe PMC Scholia
209. Jiang W, Wells NJ, Hunter T.; ''Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.''; PubMed Europe PMC Scholia
210. Leng X, Noble M, Adams PD, Qin J, Harper JW.; ''Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4.''; PubMed Europe PMC Scholia
211. Zheng Y, Asara JM, Tyner AL.; ''Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 CRK-associated substrate.''; PubMed Europe PMC Scholia
212. Orend G, Hunter T, Ruoslahti E.; ''Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells.''; PubMed Europe PMC Scholia
213. Bagui TK, Jackson RJ, Agrawal D, Pledger WJ.; ''Analysis of cyclin D3-cdk4 complexes in fibroblasts expressing and lacking p27(kip1) and p21(cip1).''; PubMed Europe PMC Scholia
214. Tedesco D, Lukas J, Reed SI.; ''The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2).''; PubMed Europe PMC Scholia
215. Yu B, Lane ME, Pestell RG, Albanese C, Wadler S.; ''Downregulation of cyclin D1 alters cdk 4- and cdk 2-specific phosphorylation of retinoblastoma protein.''; PubMed Europe PMC Scholia
216. Agger K, Cloos PA, Rudkjaer L, Williams K, Andersen G, Christensen J, Helin K.; ''The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence.''; PubMed Europe PMC Scholia
217. Ono H, Basson MD, Ito H.; ''PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling.''; PubMed Europe PMC Scholia
218. Reynisdóttir I, Massagué J.; ''The subcellular locations of p15(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with cdk4 and cdk2.''; PubMed Europe PMC Scholia
219. Dietrich N, Bracken AP, Trinh E, Schjerling CK, Koseki H, Rappsilber J, Helin K, Hansen KH.; ''Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus.''; PubMed Europe PMC Scholia
220. Castro NE, Lange CA.; ''Breast tumor kinase and extracellular signal-regulated kinase 5 mediate Met receptor signaling to cell migration in breast cancer cells.''; PubMed Europe PMC Scholia
221. Lundberg AS, Weinberg RA.; ''Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes.''; PubMed Europe PMC Scholia
222. Bertoli C, Klier S, McGowan C, Wittenberg C, de Bruin RA.; ''Chk1 inhibits E2F6 repressor function in response to replication stress to maintain cell-cycle transcription.''; PubMed Europe PMC Scholia
223. Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, Helin K.; ''EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.''; PubMed Europe PMC Scholia
224. Galaktionov K, Chen X, Beach D.; ''Cdc25 cell-cycle phosphatase as a target of c-myc.''; PubMed Europe PMC Scholia
225. DeGregori J, Kowalik T, Nevins JR.; ''Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes.''; PubMed Europe PMC Scholia
226. Ohtani K, DeGregori J, Leone G, Herendeen DR, Kelly TJ, Nevins JR.; ''Expression of the HsOrc1 gene, a human ORC1 homolog, is regulated by cell proliferation via the E2F transcription factor.''; PubMed Europe PMC Scholia
227. Vigo E, Müller H, Prosperini E, Hateboer G, Cartwright P, Moroni MC, Helin K.; ''CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase.''; PubMed Europe PMC Scholia
228. Chu I, Sun J, Arnaout A, Kahn H, Hanna W, Narod S, Sun P, Tan CK, Hengst L, Slingerland J.; ''p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2.''; PubMed Europe PMC Scholia
229. Hiebert SW.; ''Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression.''; PubMed Europe PMC Scholia
230. Goel RK, Lukong KE.; ''Tracing the footprints of the breast cancer oncogene BRK - Past till present.''; PubMed Europe PMC Scholia
231. Ohtani N, Zebedee Z, Huot TJ, Stinson JA, Sugimoto M, Ohashi Y, Sharrocks AD, Peters G, Hara E.; ''Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence.''; PubMed Europe PMC Scholia
232. Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF.; ''Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing.''; PubMed Europe PMC Scholia
233. Ikeda O, Mizushima A, Sekine Y, Yamamoto C, Muromoto R, Nanbo A, Oritani K, Yoshimura A, Matsuda T.; ''Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells.''; PubMed Europe PMC Scholia
234. Ikeda O, Sekine Y, Mizushima A, Nakasuji M, Miyasaka Y, Yamamoto C, Muromoto R, Nanbo A, Oritani K, Yoshimura A, Matsuda T.; ''Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells.''; PubMed Europe PMC Scholia
235. Zheng Y, Peng M, Wang Z, Asara JM, Tyner AL.; ''Protein tyrosine kinase 6 directly phosphorylates AKT and promotes AKT activation in response to epidermal growth factor.''; PubMed Europe PMC Scholia
236. Chen HY, Shen CH, Tsai YT, Lin FC, Huang YP, Chen RH.; ''Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin.''; PubMed Europe PMC Scholia
237. Ganoth D, Bornstein G, Ko TK, Larsen B, Tyers M, Pagano M, Hershko A.; ''The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27.''; PubMed Europe PMC Scholia
238. Vidal A, Koff A.; ''Cell-cycle inhibitors: three families united by a common cause.''; PubMed Europe PMC Scholia
239. Walter J, Newport J.; ''Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha.''; PubMed Europe PMC Scholia
240. Li Y, Pursell ZF, Linn S.; ''Identification and cloning of two histone fold motif-containing subunits of HeLa DNA polymerase epsilon.''; PubMed Europe PMC Scholia
241. Clifton AD, Young PR, Cohen P.; ''A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress.''; PubMed Europe PMC Scholia
242. Ben-Levy R, Leighton IA, Doza YN, Attwood P, Morrice N, Marshall CJ, Cohen P.; ''Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2.''; PubMed Europe PMC Scholia
243. Montagnoli A, Fiore F, Eytan E, Carrano AC, Draetta GF, Hershko A, Pagano M.; ''Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation.''; PubMed Europe PMC Scholia
244. Wu L, Timmers C, Maiti B, Saavedra HI, Sang L, Chong GT, Nuckolls F, Giangrande P, Wright FA, Field SJ, Greenberg ME, Orkin S, Nevins JR, Robinson ML, Leone G.; ''The E2F1-3 transcription factors are essential for cellular proliferation.''; PubMed Europe PMC Scholia
245. Vijayachandra K, Lee J, Glick AB.; ''Smad3 regulates senescence and malignant conversion in a mouse multistage skin carcinogenesis model.''; PubMed Europe PMC Scholia
246. Gao Y, Cimica V, Reich NC.; ''Suppressor of cytokine signaling 3 inhibits breast tumor kinase activation of STAT3.''; PubMed Europe PMC Scholia
247. Takekawa M, Tatebayashi K, Saito H.; ''Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases.''; PubMed Europe PMC Scholia
248. Moiseeva O, Mallette FA, Mukhopadhyay UK, Moores A, Ferbeyre G.; ''DNA damage signaling and p53-dependent senescence after prolonged beta-interferon stimulation.''; PubMed Europe PMC Scholia
249. Kotake Y, Cao R, Viatour P, Sage J, Zhang Y, Xiong Y.; ''pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene.''; PubMed Europe PMC Scholia
250. Lal A, Kim HH, Abdelmohsen K, Kuwano Y, Pullmann R, Srikantan S, Subrahmanyam R, Martindale JL, Yang X, Ahmed F, Navarro F, Dykxhoorn D, Lieberman J, Gorospe M.; ''p16(INK4a) translation suppressed by miR-24.''; PubMed Europe PMC Scholia
251. Kardinal C, Dangers M, Kardinal A, Koch A, Brandt DT, Tamura T, Welte K.; ''Tyrosine phosphorylation modulates binding preference to cyclin-dependent kinases and subcellular localization of p27Kip1 in the acute promyelocytic leukemia cell line NB4.''; PubMed Europe PMC Scholia
252. Cobrinik D.; ''Pocket proteins and cell cycle control.''; PubMed Europe PMC Scholia
253. Fan G, Lin G, Lucito R, Tonks NK.; ''Protein-tyrosine phosphatase 1B antagonized signaling by insulin-like growth factor-1 receptor and kinase BRK/PTK6 in ovarian cancer cells.''; PubMed Europe PMC Scholia
254. Aprelikova O, Xiong Y, Liu ET.; ''Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by the CDK-activating kinase.''; PubMed Europe PMC Scholia
255. Sgouras DN, Athanasiou MA, Beal GJ, Fisher RJ, Blair DG, Mavrothalassitis GJ.; ''ERF: an ETS domain protein with strong transcriptional repressor activity, can suppress ets-associated tumorigenesis and is regulated by phosphorylation during cell cycle and mitogenic stimulation.''; PubMed Europe PMC Scholia

History

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Compare	Revision	Action	Time	User	Comment
	114646	view	16:11, 25 January 2021	ReactomeTeam	Reactome version 75
	113094	view	11:15, 2 November 2020	ReactomeTeam	Reactome version 74
	112328	view	15:25, 9 October 2020	ReactomeTeam	Reactome version 73
	112225	view	14:39, 2 October 2020	DeSl	Ontology Term : 'M/G1 transition pathway' added !
	101227	view	11:12, 1 November 2018	ReactomeTeam	reactome version 66
	100765	view	20:38, 31 October 2018	ReactomeTeam	reactome version 65
	100309	view	19:15, 31 October 2018	ReactomeTeam	reactome version 64
	99855	view	15:59, 31 October 2018	ReactomeTeam	reactome version 63
	99413	view	14:35, 31 October 2018	ReactomeTeam	reactome version 62 (2nd attempt)
	93757	view	13:34, 16 August 2017	ReactomeTeam	reactome version 61
	93279	view	11:19, 9 August 2017	ReactomeTeam	reactome version 61
	86357	view	09:16, 11 July 2016	ReactomeTeam	reactome version 56
	83315	view	10:46, 18 November 2015	ReactomeTeam	Version54
	81454	view	12:59, 21 August 2015	ReactomeTeam	Version53
	76928	view	08:20, 17 July 2014	ReactomeTeam	Fixed remaining interactions
	76633	view	12:00, 16 July 2014	ReactomeTeam	Fixed remaining interactions
	76130	view	12:48, 11 June 2014	Anwesha
	76129	view	12:44, 11 June 2014	ReactomeTeam	Adding missing reactome URL
	75666	view	10:57, 10 June 2014	ReactomeTeam	Reactome 48 Update
	75021	view	13:53, 8 May 2014	Anwesha	Fixing comment source for displaying WikiPathways description
	74665	view	08:43, 30 April 2014	ReactomeTeam	Reactome46
	68884	view	17:26, 8 July 2013	MaintBot	Updated to 2013 gpml schema
	44912	view	10:35, 6 October 2011	MartijnVanIersel	Ontology Term : 'cell cycle pathway, mitotic' added !
	42076	view	21:55, 4 March 2011	MaintBot	Automatic update
	39884	view	05:54, 21 January 2011	MaintBot	New pathway

External references

DataNodes

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Name	Type	Database reference	Comment
26S proteasome	Complex	REACT_7467 (Reactome)
ADP	Metabolite	CHEBI:16761 (ChEBI)
ATP	Metabolite	CHEBI:15422 (ChEBI)
Aborted replication complex	Complex	REACT_2817 (Reactome)
CAK	Complex	REACT_5717 (Reactome)
CCNA	Protein	REACT_5498 (Reactome)
CCNB1	Protein	P14635 (Uniprot-TrEMBL)
CCNE1	Protein	P24864 (Uniprot-TrEMBL)
CCNE2	Protein	O96020 (Uniprot-TrEMBL)
CCNH	Protein	P51946 (Uniprot-TrEMBL)
CDC25A	Protein	P30304 (Uniprot-TrEMBL)
CDC45	Protein	O75419 (Uniprot-TrEMBL)
CDC45	Protein	O75419 (Uniprot-TrEMBL)
CDC6	Protein	Q99741 (Uniprot-TrEMBL)
CDC6	Protein	Q99741 (Uniprot-TrEMBL)
CDC7	Protein	O00311 (Uniprot-TrEMBL)
CDK DDK Mcm10 pre-replicative complex	Complex	REACT_2458 (Reactome)
CDK1	Protein	P06493 (Uniprot-TrEMBL)
CDK1	Protein	P06493 (Uniprot-TrEMBL)
CDK2	Protein	P24941 (Uniprot-TrEMBL)
CDK2	Protein	P24941 (Uniprot-TrEMBL)
CDK4	Protein	P11802 (Uniprot-TrEMBL)
CDK6	Protein	Q00534 (Uniprot-TrEMBL)
CDK7	Protein	P50613 (Uniprot-TrEMBL)
CDKN1A	Protein	P38936 (Uniprot-TrEMBL)
CDKN1A	Protein	P38936 (Uniprot-TrEMBL)
CDKN1B	Protein	P46527 (Uniprot-TrEMBL)
CDKN1B	Protein	P46527 (Uniprot-TrEMBL)
CDKN2B	Protein	P42772 (Uniprot-TrEMBL)
CDKN2C	Protein	P42773 (Uniprot-TrEMBL)
CDKN2D	Protein	P55273 (Uniprot-TrEMBL)
CDK	Complex	REACT_5476 (Reactome)
CDT1	Protein	Q9H211 (Uniprot-TrEMBL)
CDT1	Protein	Q9H211 (Uniprot-TrEMBL)
CKS1B	Protein	P61024 (Uniprot-TrEMBL)
CKS1B	Protein	P61024 (Uniprot-TrEMBL)
CUL1	Protein	Q13616 (Uniprot-TrEMBL)
Cdc45 CDK DDK Mcm10 pre-replicative complex	Complex	REACT_4546 (Reactome)
Cdk4/6 INK4A complex	Complex	REACT_8076 (Reactome)
Cdk4/6		REACT_4552 (Reactome)
Cdk4/6	Protein	REACT_8720 (Reactome)
Cyclin B Cdk1 complex	Complex	REACT_4583 (Reactome)
Cyclin D CDK4/6 p21/p27 complex	Complex	REACT_2341 (Reactome)
Cyclin D Cdk4/6 p21/p27	Complex	REACT_2453 (Reactome)
Cyclin D phospho-CDK4/6 p21/p27	Complex	REACT_3625 (Reactome)
Cyclin D	Protein	REACT_8063 (Reactome)
Cyclin E Cdk2 p21/p27 complex	Complex	REACT_3804 (Reactome)
Cyclin E Cdk2 complex	Complex	REACT_3296 (Reactome)
Cyclin E Cdk2 complexes	Complex	REACT_5247 (Reactome)
Cyclin E Phosho-Cdk2	Complex	REACT_9167 (Reactome)
Cyclin E Phospho-Cdk2	Complex	REACT_9136 (Reactome)
Cyclin E phospho-Cdk2 Complex	Complex	REACT_4112 (Reactome)
Cyclin E phospho-Cdk2	Complex	REACT_9190 (Reactome)
Cyclin E/A Cdk2 multiubiquitinated phospho-p27/p21 SCF	Complex	REACT_9266 (Reactome)
Cyclin E/A Cdk2 p27/p21 complex	Complex	REACT_9314 (Reactome)
Cyclin E/A Cdk2 phospho-p27/p21 SCF	Complex	REACT_9193 (Reactome)
Cyclin E/A Cdk2 phospho-p27/p21	Complex	REACT_9321 (Reactome)
Cyclin E/A Cdk2	Complex	REACT_9091 (Reactome)
Cyclin E1 Cdk2 complex	Complex	REACT_4601 (Reactome)
Cyclin E1 phospho-Cdk2 complex	Complex	REACT_2714 (Reactome)
Cyclin E2 Cdk2 complex	Complex	REACT_5296 (Reactome)
Cyclin E2 phospho-Cdk2 complex	Complex	REACT_3967 (Reactome)
Cyclin E	Protein	REACT_5284 (Reactome)
DBF4	Protein	Q9UBU7 (Uniprot-TrEMBL)
DDK	Complex	REACT_4813 (Reactome)
DNA Replication Factor A	Complex	REACT_5149 (Reactome)
DNA polymerase alpha primase DNA polymerase alpha origin complex	Complex	REACT_3167 (Reactome)
DNA polymerase alpha primase	Complex	REACT_3725 (Reactome)
DNA polymerase epsilon origin complex	Complex	REACT_3283 (Reactome)
DNA polymerase epsilon	Complex	REACT_4621 (Reactome)
DP-1 E2F1/2/3	Complex	REACT_76628 (Reactome)
DREAM complex	Complex	REACT_111426 (Reactome)
DYRK1A	Protein	Q13627 (Uniprot-TrEMBL)
E2F1 TFDP1	Complex	REACT_5400 (Reactome)
E2F1	Protein	Q01094 (Uniprot-TrEMBL)
E2F1 targets	Protein	REACT_22550 (Reactome)
E2F1	Protein	Q01094 (Uniprot-TrEMBL)
E2F2	Protein	Q14209 (Uniprot-TrEMBL)
E2F3	Protein	O00716 (Uniprot-TrEMBL)
E2F4 TFDP1,TFDP2	Complex	REACT_111631 (Reactome)
E2F4	Protein	Q16254 (Uniprot-TrEMBL)
E2F4/5 DP1/2	Complex	REACT_111584 (Reactome)
E2F5	Protein	Q15329 (Uniprot-TrEMBL)
H2O	Metabolite	CHEBI:15377 (ChEBI)
HDAC1 RBL1 E2F4 TFDP1,TFDP2	Complex	REACT_111485 (Reactome)
HDAC1 RBL2 E2F4/5 DP1/2	Complex	REACT_111840 (Reactome)
HDAC1	Protein	Q13547 (Uniprot-TrEMBL)
HDAC1	Protein	Q13547 (Uniprot-TrEMBL)
INK4A		REACT_8915 (Reactome)
LIN37	Protein	Q96GY3 (Uniprot-TrEMBL)
LIN52	Protein	Q52LA3 (Uniprot-TrEMBL)
LIN54	Protein	Q6MZP7 (Uniprot-TrEMBL)
LIN9	Protein	Q5TKA1 (Uniprot-TrEMBL)
MAX	Protein	P61244 (Uniprot-TrEMBL)
MCM10	Protein	Q7L590 (Uniprot-TrEMBL)
MCM10	Protein	Q7L590 (Uniprot-TrEMBL)
MCM2	Protein	P49736 (Uniprot-TrEMBL)
MCM3	Protein	P25205 (Uniprot-TrEMBL)
MCM4	Protein	P33991 (Uniprot-TrEMBL)
MCM5	Protein	P33992 (Uniprot-TrEMBL)
MCM6	Protein	Q14566 (Uniprot-TrEMBL)
MCM7	Protein	P33993 (Uniprot-TrEMBL)
MCM8	Protein	Q9UJA3 (Uniprot-TrEMBL)
MNAT1	Protein	P51948 (Uniprot-TrEMBL)
MYBL2	Protein	P10244 (Uniprot-TrEMBL)
MYC	Protein	P01106 (Uniprot-TrEMBL)
Mcm10 active pre-replicative complex	Complex	REACT_2683 (Reactome)
Mcm10 pre-replicative complex	Complex	REACT_5685 (Reactome)
Mcm2-7 complex	Complex	REACT_4763 (Reactome)
MuvB complex	Complex	REACT_111706 (Reactome)
Myc/Max heterodimer	Complex	REACT_9233 (Reactome)
ORC origin cyclin B cdk1 complex	Complex	REACT_4235 (Reactome)
ORC origin	Complex	REACT_3844 (Reactome)
ORC1	Protein	Q13415 (Uniprot-TrEMBL)
ORC2	Protein	Q13416 (Uniprot-TrEMBL)
ORC3	Protein	Q9UBD5 (Uniprot-TrEMBL)
ORC4	Protein	O43929 (Uniprot-TrEMBL)
ORC5	Protein	O43913 (Uniprot-TrEMBL)
ORC6	Protein	Q9Y5N6 (Uniprot-TrEMBL)
PCNA	Protein	P12004 (Uniprot-TrEMBL)
PKMYT1	Protein	Q99640 (Uniprot-TrEMBL)
POLA1	Protein	P09884 (Uniprot-TrEMBL)
POLA2	Protein	Q14181 (Uniprot-TrEMBL)
POLE	Protein	Q07864 (Uniprot-TrEMBL)
POLE2	Protein	P56282 (Uniprot-TrEMBL)
PP2A	Complex	REACT_111616 (Reactome)
PP2A	Complex	REACT_111771 (Reactome)
PPP2R3B	Protein	Q9Y5P8 (Uniprot-TrEMBL)
PRIM1	Protein	P49642 (Uniprot-TrEMBL)
PRIM2	Protein	P49643 (Uniprot-TrEMBL)
PSMA1	Protein	P25786 (Uniprot-TrEMBL)
PSMA2	Protein	P25787 (Uniprot-TrEMBL)
PSMA3	Protein	P25788 (Uniprot-TrEMBL)
PSMA4	Protein	P25789 (Uniprot-TrEMBL)
PSMA5	Protein	P28066 (Uniprot-TrEMBL)
PSMA6	Protein	P60900 (Uniprot-TrEMBL)
PSMA7	Protein	O14818 (Uniprot-TrEMBL)
PSMB1	Protein	P20618 (Uniprot-TrEMBL)
PSMB10	Protein	P40306 (Uniprot-TrEMBL)
PSMB2	Protein	P49721 (Uniprot-TrEMBL)
PSMB3	Protein	P49720 (Uniprot-TrEMBL)
PSMB4	Protein	P28070 (Uniprot-TrEMBL)
PSMB5	Protein	P28074 (Uniprot-TrEMBL)
PSMB6	Protein	P28072 (Uniprot-TrEMBL)
PSMB7	Protein	Q99436 (Uniprot-TrEMBL)
PSMB8	Protein	P28062 (Uniprot-TrEMBL)
PSMB9	Protein	P28065 (Uniprot-TrEMBL)
PSMC1	Protein	P62191 (Uniprot-TrEMBL)
PSMC2	Protein	P35998 (Uniprot-TrEMBL)
PSMC3	Protein	P17980 (Uniprot-TrEMBL)
PSMC4	Protein	P43686 (Uniprot-TrEMBL)
PSMC5	Protein	P62195 (Uniprot-TrEMBL)
PSMC6	Protein	P62333 (Uniprot-TrEMBL)
PSMD1	Protein	Q99460 (Uniprot-TrEMBL)
PSMD10	Protein	O75832 (Uniprot-TrEMBL)
PSMD11	Protein	O00231 (Uniprot-TrEMBL)
PSMD12	Protein	O00232 (Uniprot-TrEMBL)
PSMD13	Protein	Q9UNM6 (Uniprot-TrEMBL)
PSMD14	Protein	O00487 (Uniprot-TrEMBL)
PSMD2	Protein	Q13200 (Uniprot-TrEMBL)
PSMD3	Protein	O43242 (Uniprot-TrEMBL)
PSMD4	Protein	P55036 (Uniprot-TrEMBL)
PSMD5	Protein	Q16401 (Uniprot-TrEMBL)
PSMD6	Protein	Q15008 (Uniprot-TrEMBL)
PSMD7	Protein	P51665 (Uniprot-TrEMBL)
PSMD8	Protein	P48556 (Uniprot-TrEMBL)
PSMD9	Protein	O00233 (Uniprot-TrEMBL)
PSME1	Protein	Q06323 (Uniprot-TrEMBL)
PSME2	Protein	Q9UL46 (Uniprot-TrEMBL)
PSME3	Protein	P61289 (Uniprot-TrEMBL)
PSMF1	Protein	Q92530 (Uniprot-TrEMBL)
Pi	Metabolite	CHEBI:18367 (ChEBI)
Pi	Metabolite	CHEBI:18367 (ChEBI)
RB1	Protein	P06400 (Uniprot-TrEMBL)
RB1	Protein	P06400 (Uniprot-TrEMBL)
RBBP4	Protein	Q09028 (Uniprot-TrEMBL)
RBL1 Cyclin E/A CDK2	Complex	REACT_111400 (Reactome)
RBL1 E2F4 DP1/2 Cyclin E/A CDK2	Complex	REACT_111813 (Reactome)
RBL1 E2F4 TFDP1,TFDP2	Complex	REACT_111376 (Reactome)
RBL1	Protein	P28749 (Uniprot-TrEMBL)
RBL1	Protein	P28749 (Uniprot-TrEMBL)
RBL2 Cyclin E/A CDK2	Complex	REACT_111575 (Reactome)
RBL2 E2F4/5 DP1/2 Cyclin E/A CDK2	Complex	REACT_111339 (Reactome)
RBL2 E2F4/5 DP1/2	Complex	REACT_111674 (Reactome)
RBL2	Protein	Q08999 (Uniprot-TrEMBL)
RBL2	Protein	Q08999 (Uniprot-TrEMBL)
RNA primer-DNA primer origin duplex with DNA damage	Complex	REACT_2843 (Reactome)
RNA primer-DNA primer origin duplex	Complex	REACT_5497 (Reactome)
RPA Cdc45 CDK DDK Mcm10 pre-replicative complex	Complex	REACT_2568 (Reactome)
RPA1	Protein	P27694 (Uniprot-TrEMBL)
RPA2	Protein	P15927 (Uniprot-TrEMBL)
RPA3	Protein	P35244 (Uniprot-TrEMBL)
RPA4	Protein	Q13156 (Uniprot-TrEMBL)
RPS27A	Protein	P62979 (Uniprot-TrEMBL)
Rb-E2F1/2/3 DP-1 complex	Complex	REACT_4483 (Reactome)
Rb1 RNA primer-DNA primer origin duplex with DNA damage	Complex	REACT_3869 (Reactome)
SCF	Complex	REACT_9182 (Reactome)
SCF	Complex	REACT_9339 (Reactome)
SKP1	Protein	P63208 (Uniprot-TrEMBL)
SKP2	Protein	Q13309 (Uniprot-TrEMBL)
TFDP1	Protein	Q14186 (Uniprot-TrEMBL)
TFDP2	Protein	Q14188 (Uniprot-TrEMBL)
TOP2A	Protein	P11388 (Uniprot-TrEMBL)
UBA52	Protein	P62987 (Uniprot-TrEMBL)
UBB	Protein	P0CG47 (Uniprot-TrEMBL)
UBC	Protein	P0CG48 (Uniprot-TrEMBL)
Ub-p-T401,S672,1035-RBL2	Complex	REACT_111808 (Reactome)
WEE1	Protein	P30291 (Uniprot-TrEMBL)
origin of replication		REACT_3087 (Reactome)
p-CDK2	Protein	P24941 (Uniprot-TrEMBL)
p-MuvB complex	Complex	REACT_111785 (Reactome)
p-RB1	Protein	P06400 (Uniprot-TrEMBL)	The pRB C-terminus contains a cluster of seven candidate in vivo cdk phosphorylation sites (residues 795, 807, 811, 821, and 826) and is phosphorylated in vitro by cyclin A, cyclin E, and cyclin D-associated kinases.
p-S130-CDKN1A	Protein	P38936 (Uniprot-TrEMBL)
p-S28-LIN52	Protein	Q52LA3 (Uniprot-TrEMBL)
p-S795-RB1	Protein	P06400 (Uniprot-TrEMBL)
p-T160-CDK2	Protein	P24941 (Uniprot-TrEMBL)
p-T187-CDKN1B	Protein	P46527 (Uniprot-TrEMBL)
p-T369,S640,S964,S975-RBL1	Protein	P28749 (Uniprot-TrEMBL)
p-T401,S672,1035-RBL2 SCF	Complex	REACT_111614 (Reactome)
p-T401,S672,S1035-RBL2	Protein	Q08999 (Uniprot-TrEMBL)
p-T401,S672,S1035-RBL2	Protein	Q08999 (Uniprot-TrEMBL)
p16-INK4a	Protein	P42771 (Uniprot-TrEMBL)
p21/p27	Protein	REACT_8233 (Reactome)
p21/p27	Protein	REACT_8306 (Reactome)
phosphorylated Mcm2-7 complex	Complex	REACT_4259 (Reactome)
pre-replicative complex	Complex	REACT_4388 (Reactome)
ubiquitin	Protein	REACT_3995 (Reactome)

Annotated Interactions

View all...

Source	Target	Type	Database reference	Comment
26S proteasome		mim-catalysis	REACT_9034 (Reactome)
	ADP	Arrow	REACT_111075 (Reactome)
	ADP	Arrow	REACT_111206 (Reactome)
	ADP	Arrow	REACT_111248 (Reactome)
	ADP	Arrow	REACT_1657 (Reactome)
	ADP	Arrow	REACT_1882 (Reactome)
	ADP	Arrow	REACT_2081 (Reactome)
	ADP	Arrow	REACT_384 (Reactome)
	ADP	Arrow	REACT_773 (Reactome)
	ADP	Arrow	REACT_8993 (Reactome)
	ADP	Arrow	REACT_8998 (Reactome)
	ADP	Arrow	REACT_9067 (Reactome)
	ADP	Arrow	REACT_907 (Reactome)
	ADP	Arrow	REACT_96 (Reactome)
ATP			REACT_111075 (Reactome)
ATP			REACT_111206 (Reactome)
ATP			REACT_111248 (Reactome)
ATP			REACT_1657 (Reactome)
ATP			REACT_1882 (Reactome)
ATP			REACT_2081 (Reactome)
ATP			REACT_384 (Reactome)
ATP			REACT_773 (Reactome)
ATP			REACT_8993 (Reactome)
ATP			REACT_8998 (Reactome)
ATP			REACT_9067 (Reactome)
ATP			REACT_907 (Reactome)
ATP			REACT_96 (Reactome)
CAK		mim-catalysis	REACT_9067 (Reactome)
CAK		mim-catalysis	REACT_96 (Reactome)
	CCNA	Arrow	REACT_111173 (Reactome)
	CDC25A	Arrow	REACT_111167 (Reactome)
	CDC25A	Arrow	REACT_1205 (Reactome)
CDC25A		mim-catalysis	REACT_592 (Reactome)
CDC45			REACT_135 (Reactome)
	CDC6	Arrow	REACT_111167 (Reactome)
CDK DDK Mcm10 pre-replicative complex			REACT_135 (Reactome)
	CDK1	Arrow	REACT_111173 (Reactome)
CDK2			REACT_1683 (Reactome)
CDK			REACT_2227 (Reactome)
	CDT1	Arrow	REACT_951 (Reactome)
CKS1B			REACT_9017 (Reactome)
Cdc45 CDK DDK Mcm10 pre-replicative complex			REACT_789 (Reactome)
Cdk4/6 INK4A complex		TBar	REACT_2081 (Reactome)
Cdk4/6			REACT_2081 (Reactome)
Cdk4/6			REACT_7947 (Reactome)
	Cyclin B Cdk1 complex	Arrow	REACT_1205 (Reactome)
Cyclin B Cdk1 complex			REACT_555 (Reactome)
	Cyclin D CDK4/6 p21/p27 complex	Arrow	REACT_2081 (Reactome)
Cyclin D Cdk4/6 p21/p27			REACT_96 (Reactome)
	Cyclin D phospho-CDK4/6 p21/p27	Arrow	REACT_96 (Reactome)
Cyclin D phospho-CDK4/6 p21/p27		mim-catalysis	REACT_111206 (Reactome)
Cyclin D phospho-CDK4/6 p21/p27		mim-catalysis	REACT_111248 (Reactome)
Cyclin D phospho-CDK4/6 p21/p27		mim-catalysis	REACT_1882 (Reactome)
Cyclin D			REACT_2081 (Reactome)
	Cyclin E Cdk2 complexes	Arrow	REACT_592 (Reactome)
Cyclin E Cdk2 complexes			REACT_334 (Reactome)
Cyclin E Cdk2 complexes			REACT_773 (Reactome)
Cyclin E Cdk2 complexes			REACT_9067 (Reactome)
	Cyclin E Phosho-Cdk2	Arrow	REACT_9067 (Reactome)
Cyclin E Phosho-Cdk2			REACT_9050 (Reactome)
Cyclin E Phospho-Cdk2			REACT_8993 (Reactome)
Cyclin E Phospho-Cdk2		mim-catalysis	REACT_8993 (Reactome)
	Cyclin E phospho-Cdk2	Arrow	REACT_8993 (Reactome)
	Cyclin E phospho-Cdk2 Complex	Arrow	REACT_773 (Reactome)
Cyclin E phospho-Cdk2 Complex			REACT_592 (Reactome)
Cyclin E/A Cdk2 multiubiquitinated phospho-p27/p21 SCF		mim-catalysis	REACT_9026 (Reactome)
Cyclin E/A Cdk2 p27/p21 complex			REACT_8998 (Reactome)
Cyclin E/A Cdk2 p27/p21 complex		mim-catalysis	REACT_8998 (Reactome)
Cyclin E/A Cdk2 phospho-p27/p21 SCF			REACT_9026 (Reactome)
	Cyclin E/A Cdk2 phospho-p27/p21	Arrow	REACT_8998 (Reactome)
Cyclin E/A Cdk2 phospho-p27/p21			REACT_9060 (Reactome)
	Cyclin E/A Cdk2	Arrow	REACT_9034 (Reactome)
Cyclin E/A Cdk2			REACT_111039 (Reactome)
Cyclin E/A Cdk2			REACT_111079 (Reactome)
Cyclin E/A Cdk2			REACT_111109 (Reactome)
Cyclin E/A Cdk2			REACT_111202 (Reactome)
Cyclin E1 Cdk2 complex			REACT_1657 (Reactome)
	Cyclin E1 phospho-Cdk2 complex	Arrow	REACT_1657 (Reactome)
Cyclin E2 Cdk2 complex			REACT_384 (Reactome)
	Cyclin E2 phospho-Cdk2 complex	Arrow	REACT_384 (Reactome)
Cyclin E			REACT_1683 (Reactome)
DDK			REACT_2227 (Reactome)
DDK		mim-catalysis	REACT_907 (Reactome)
DNA Replication Factor A			REACT_789 (Reactome)
	DNA polymerase alpha primase	Arrow	REACT_1408 (Reactome)
DNA polymerase alpha primase			REACT_929 (Reactome)
DNA polymerase epsilon origin complex			REACT_929 (Reactome)
DNA polymerase epsilon			REACT_1344 (Reactome)
	DP-1 E2F1/2/3	Arrow	REACT_1882 (Reactome)
DREAM complex		TBar	REACT_111167 (Reactome)
DYRK1A		mim-catalysis	REACT_111075 (Reactome)
E2F1 TFDP1		Arrow	REACT_22145 (Reactome)
E2F1 TFDP1			REACT_1277 (Reactome)
	E2F1	Arrow	REACT_111167 (Reactome)
	E2F1	Arrow	REACT_111173 (Reactome)
	E2F4 TFDP1,TFDP2	Arrow	REACT_111248 (Reactome)
	E2F4/5 DP1/2	Arrow	REACT_111206 (Reactome)
H2O			REACT_111148 (Reactome)
H2O			REACT_111170 (Reactome)
H2O			REACT_592 (Reactome)
HDAC1 RBL1 E2F4 TFDP1,TFDP2		TBar	REACT_111173 (Reactome)
HDAC1 RBL2 E2F4/5 DP1/2		TBar	REACT_111173 (Reactome)
HDAC1			REACT_111037 (Reactome)
HDAC1			REACT_111090 (Reactome)
INK4A			REACT_7947 (Reactome)
MCM10			REACT_541 (Reactome)
	MYBL2	Arrow	REACT_111173 (Reactome)
	Mcm10 active pre-replicative complex	Arrow	REACT_951 (Reactome)
Mcm10 active pre-replicative complex			REACT_2227 (Reactome)
Mcm2-7 complex			REACT_907 (Reactome)
MuvB complex			REACT_111075 (Reactome)
Myc/Max heterodimer		Arrow	REACT_9013 (Reactome)
ORC origin			REACT_555 (Reactome)
	PCNA	Arrow	REACT_111167 (Reactome)
PKMYT1		mim-catalysis	REACT_1657 (Reactome)
PKMYT1		mim-catalysis	REACT_384 (Reactome)
PP2A		mim-catalysis	REACT_111148 (Reactome)
PP2A		mim-catalysis	REACT_111170 (Reactome)
PP2A		mim-catalysis	REACT_421 (Reactome)
	Pi	Arrow	REACT_111148 (Reactome)
	Pi	Arrow	REACT_111170 (Reactome)
	Pi	Arrow	REACT_592 (Reactome)
RB1			REACT_9050 (Reactome)
RBL1 E2F4 TFDP1,TFDP2			REACT_111039 (Reactome)
RBL1 E2F4 TFDP1,TFDP2			REACT_111090 (Reactome)
RBL1 E2F4 TFDP1,TFDP2			REACT_111248 (Reactome)
	RBL1	Arrow	REACT_111148 (Reactome)
	RBL1	Arrow	REACT_111167 (Reactome)
RBL1			REACT_111202 (Reactome)
RBL2 E2F4/5 DP1/2			REACT_111037 (Reactome)
RBL2 E2F4/5 DP1/2			REACT_111109 (Reactome)
RBL2 E2F4/5 DP1/2			REACT_111206 (Reactome)
RBL2 E2F4/5 DP1/2			REACT_111236 (Reactome)
	RBL2	Arrow	REACT_111170 (Reactome)
RBL2			REACT_111079 (Reactome)
			REACT_111037 (Reactome)	p130 (RBL2) in complex with E2F4 or E2F5 and DP1 or DP2 recruits histone deacetylase HDAC1, probably in complex with other chromatin modification factors, and represses transcription of E2F target promoters during G0 in quiescent cells.
			REACT_111039 (Reactome)	p107 (RBL1) in complex with E2F4 and DP1/2 binds to cyclin A or cyclin E in complex with CDK2 through its conserved LFG pocket domain motif and amino terminus, leading to inhibition of CDK2 kinase activity and suppression of cellular growth.
			REACT_111075 (Reactome)	LIN52 subunit of MuvB complex is phosphorylated by the protein kinase DYRK1A on the serine residue S28, promoting association of MuvB with p130 (RBL2). From model organism studies, DYRK proteins are known to function in cell cycle regulation, differentiation and stress response.
			REACT_111079 (Reactome)	p130 (RBL2) is able to bind complexes of CDK2 with either cyclin A or cyclin E through the cyclin-binding LFG motif within the pocket domain, which is conserved in p107 (RBL1) and p21/WAF1/Cip1 family of cyclin-dependent kinases. In addition to LFG motif, amino terminal region of p130 (RBL2), conserved in p107 (RBL1), is necessary for inhibition of CDK2 kinase activity. Presence of E2F is not required for this interaction.
			REACT_111089 (Reactome)	As quiescent G0 cells reenter the cell cycle, p130 (RBL2) is phosphorylated by CDK4/6. This phosphorylated p130 (RBL2) binds ubiquitin ligase SCF (Skp2) in complex with Cks1, and is subsequently ubiquitinated and degraded similarly to p27, which is another target of SCF (Skp2).
			REACT_111090 (Reactome)	p107 (RBL1) in complex with E2F4 and DP1 or DP2 recruits histone deacetylase HDAC1 (possibly in complex with other chromatin modification proteins) through LXCXE-like motif, shared by pocket proteins, to repress transcription of E2F target genes in early G1.
			REACT_111109 (Reactome)	p130 (RBL2) in complex with E2F4/5 and DP1/2 binds to cyclin A or cyclin E in complex with CDK2 through its conserved LFG pocket domain motif and amino terminus, leading to inhibition of CDK2 kinase activity and suppression of cellular growth.
			REACT_111148 (Reactome)	Dephosphorylation of p107 (RBL1) by PP2A complex containing either PPP2R3B (B" beta) or PPP2R2A (B alpha) regulatory subunit plays a role in maintaining the equilibrium of hyperphosphorylated and hypophosphorylated p107 (RBL1), through counteracting action of cyclin dependent kinases (CDKs) throughout the cell cycle. It is assumed that PP2A dephosphorylates p107 (RBL1) on all four phosphorylation sites, but further experiments are needed to confirm this.
			REACT_111167 (Reactome)	DREAM complex is evolutionarily conserved and is reponsible for transcriptional repressession of cell cycle-regulated genes in G0 and early G1.
			REACT_111170 (Reactome)	Dephosphorylation of p130 (RBL2) by PP2A complex containing either PPP2R3B (B" beta) or PPP2R2A (B alpha) regulatory subunit plays a role in maintaining the equilibrium of hyperphosphorylated and hypophosphorylated p130 (RBL2), through counteracting action of cyclin dependent kinases (CDKs). It is assumed that PP2A dephosphorylates p130 (RBL2) on all three phosphorylation sites, but further experiments are needed to confirm this.
			REACT_111173 (Reactome)	In G0 and early G1, expression of E2F target genes such as Cyclin A, E2F1, CDC2 and MYBL2 is inhibited by complexes containing p130 (RBL2) and p107 (RBL1), respectively, and histone deacetylase HDAC1.
			REACT_111194 (Reactome)	Phosphorylated p130 (RBL2) binds SCF (Skp2) ubiquitin ligase in complex with Cks1. Phosphorylation of p130 (RBL2) serine residue S672 by CDK4/6 is critical for this interaction.
			REACT_111202 (Reactome)	p107 (RBL1) is able to bind complexes of CDK2 with either cyclin A or cyclin E, through cyclin-binding LFG motif in the pocket domain, which is conserved in p130 (RBL2) and p21/WAF1/Cip1 family of cyclin-dependent kinase inhibitors. In addition to the LFG motif, the amino terminal sequence conserved in the p107 (RBL1) and p130 (RBL2) is needed for inhibition of CDK2 kinase activity. Presence of E2F is not required for this interaction.
			REACT_111206 (Reactome)	At G1 entry from G0, p130 (RBL2) is phosphorylated on three threonine and serine residues by cyclin D1 dependent kinases CDK4 and/or CDK6, leading to dissociation of p130 (RBL2) from complexes it formed with E2F4 or E2F5 and DP1 or DP2. This is thought to promote translocation of E2F4 and E2F5, which lack nuclear localization signals, to the cytosol, allowing activating E2Fs (E2F1, E2F2 and E2F3) to bind E2F promoters and activate transcription of genes needed for G1 progression.
			REACT_111236 (Reactome)	In G0 and early G1, p130 (RBL2) bound to E2F4 or E2F5 and DP1 or DP2 associates with the MuvB complex, consisting of LIN9, LIN37, LIN52, LIN54 and RBBP4 to form evolutionarily conserved DREAM complex. Phosphorylation of LIN52 on serine residue S28 is critical for association of MuvB complex with p130 (RBL2).
			REACT_111248 (Reactome)	In late G1, cyclin D dependent kinases CDK4 and CDK6 phosphorylate RBL1 (p107) on four serine and threonine residues (S964, S975, T369 and S640), leading to dissociation of phosphorylated RBL1 (p107) from E2F4 in complex with either DP-1 or DP-2. E2F4, which lacks nuclear localization signal, is then thought to translocate to the cytosol, allowing E2F promoter sites to become occupied by activating E2Fs (E2F1, E2F2, and E2F3), resulting in transcription of E2F targets needed for cell cycle progression.
			REACT_1205 (Reactome)	At the end of this reaction, 1 molecule of 'Cyclin B:Cdk1 complex', and 1 molecule of 'Cdc25A' are present. This reaction takes place in the 'nucleus'.
			REACT_1277 (Reactome)	This set of events is inferred from annotated events in Drosophila. Rb1 is normally hyperphosphorylated by CycD/CDK4/CDK6 and Cyclin E/CDK2 for transition into S-phase. PP2A can then reverse this reaction, in this case, in response to DNA damage induced checkpoint.
			REACT_1344 (Reactome)	At the beginning of this reaction, 1 molecule of 'origin of replication', and 1 molecule of 'DNA polymerase epsilon' are present. At the end of this reaction, 1 molecule of 'DNA polymerase epsilon:origin complex' is present.
			REACT_135 (Reactome)	Once the Mcm2-7 complex has been assembled onto the origin of replication, the next step is the assembly of Cdc45, an essential replication protein, in late G1. The assembly of Cdc45 onto origins of replication forms a complex distinct from the pre-replicative complex, sometimes called the pre-initiation complex. The assembly of Cdc45 onto origins correlates with the time of initiation. Like the Mcm2-7 proteins, Cdc45 binds specifically to origins in the G1 phase of the cell cycle and then to non-origin DNA during S phase and is therefore thought to travel with the replication fork. Indeed, S. cerevisiae Cdc45 is required for DNA replication elongation as well as replication initiation. Cdc45 is required for the association of alpha DNA polymerase:primase with chromatin. Based on this observation and the observation that in S. cerevisiae, cCdc45 has been found in large complexes with some components of Mcm2-7 complex, it has been suggested that Cdc45 plays a scaffolding role at the replication fork, coupling Pol-alpha:primase to the replication fork through the helicase. Association of Cdc45 with origin DNA is regulated in the cell cycle and its association is dependent on the activity of cyclin-dependent kinases but not the Cdc7/Dbf4 kinase. In Xenopus egg extracts, association of Cdc45 with chromatin is dependent on Xmus101. TopBP1, the human homolog of Xmus1, is essential for DNA replication and interacts with DNA polymerase epsilon, one of the polymerases involved in replicating the genome. TopBP1 homologs have been found in S. cerevisiae and S. pombe. Sld3, an additional protein required for Cdc45 association with chromatin in S. cerevisiae and S. pombe, has no known human homolog.
			REACT_1408 (Reactome)	At the beginning of this reaction, 1 molecule of 'RNA primer-DNA primer:origin duplex' is present. At the end of this reaction, 1 molecule of 'DNA polymerase alpha:primase', and 1 molecule of 'RNA primer-DNA primer:origin duplex with DNA damage' are present. This reaction takes place in the 'nucleus'.
			REACT_1657 (Reactome)	At the beginning of this reaction, 1 molecule of 'ATP', and 1 molecule of 'Cyclin E1:Cdk2 complex' are present. At the end of this reaction, 1 molecule of 'Cyclin E1:phospho-Cdk2 complex', and 1 molecule of 'ADP' are present. This reaction takes place in the 'nucleoplasm' and is mediated by the 'kinase activity' of 'Myt1 kinase'.
			REACT_1683 (Reactome)	The E-type cyclins and Cyclin Dependent Kinase 2 control the transition from G1 to S phase. Cdk2 is competent to carry out the necessary reactions only when complexed with Cyclin E.
			REACT_1882 (Reactome)	Cyclin D:Cdk4 mediated phosphorylation of RB1 releases RB1 from the transcriptional regulator E2F and activates E2F function.
			REACT_2081 (Reactome)	The formation of CyclinD:CDK4/6 complexes is promoted by two proteins, p21Cip1/Waf1 and p27kip1. Activity of the cyclin-dependent kinases 4 and 6 can be inhibited by the binding of several small CDK-inhibitory proteins (CKIs).
			REACT_22145 (Reactome)	E2F1 binds to E2F binding sites on the genome activating the synthesis of the target proteins. For annotation purposes, the reactions regulated by E2F1 are grouped under this pathway and information about the target genes alone are displayed for annotation purposes. Cellular targets for activation by E2F1 include thymidylate synthetase, Rir2, Dihydrofolate reductase, Cdc2, Cyclin A1, Cdc6 (DeGregori et al., 1995), Cdt1 (Yoshida and Inoue, 2004), CDC45 (Arata et al., 2000), CDC6 (Yan et al., 1998; Ohtani et al., 1998), Cyclin E (Ohtani et al., 1996), Emi1 (Hsu et al., 2002), and Orc1 (Ohtani et al., 1997). The activation of TK2 (Dnk1) and Cdc25A by E2F1 have been inferred from similar events in Drosophila (Duronio and O'Farrell, 1994;Reis and Edgar, 2004). Rir2 protein is involved in dNTP level regulation and activation of this enzyme results in higher levels of dNTPs in anticipation of S-phase. E2F activation of Rir2 has been shown also in Drosophila by Duronio and O'Farrell (1994). E2F1 activation of CDC45 is shown in mouse cells by using human E2F1 construct (Arata et al., 2000). Cyclin E is also transcriptionally regulated by E2F1. Cyclin E protein plays important role in the transition of G1 in S-phase by associating with Cdk2 (Ohtani et al., 1996). E2F activation of PCNA has been demonstrated in Drosophila (DeGregori et al., 1995) and in some human cells by using recombinant adenovirus constructs. E2F activation of Polymerase A (Pol A) has been demonstrated in some human cells. It has also been demonstrated in Drosophila by Ohtani and Nevins (1994). It has been observed in Drosophila that E2F1 regulated expression of Orc1 stimulates ORC1-6 complex formation and binding to the origin of replication (Asano and Wharton, 1999). Orc1-6 recruit Cdc6 and Cdt1 that are required to recruit the MCM2-7 replication helicases. E2F1 regulation incorporates a feedback mechanism where in Geminin can inhibit MCM2-7 recruitment of ORC1-6 complex by interacting with Cdc6/Cdt1. The activation of Cdc25A and TK2 (Dnk1) by E2F1 has been inferred from similar events in Drosophila (Duronio RJ, O'Farrell 1994; Reis and Edgar, 2004). E2F1 activates string (Cdc25) that in turn activates Cyclin B/Cdk1. A similar phenomenon has been observed in mouse NIH 3T3 cells and in Rat1 cells.
			REACT_2227 (Reactome)	At the beginning of this reaction, 1 molecule of 'Mcm10:active pre-replicative complex', 1 molecule of 'DDK', and 1 molecule of 'CDK' are present. At the end of this reaction, 1 molecule of 'CDK:DDK:Mcm10:pre-replicative complex' is present. This reaction takes place in the 'nucleus'.
			REACT_334 (Reactome)	During G1, the activity of cyclin-dependent kinases (CDKs) is kept in check by the CDK inhibitors (CKIs) p27 and p21, thereby preventing premature entry into S phase (see Guardavaccaro and Pagano, 2006). The efficient recognition and ubiquitination of p27 by the SCF(Skp2) complex requires the formation of a trimeric complex containing p27 and cyclin E/A:Cdk2.
			REACT_384 (Reactome)	At the beginning of this reaction, 1 molecule of 'Cyclin E2:Cdk2 complex', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'Cyclin E2:phospho-Cdk2 complex', and 1 molecule of 'ADP' are present. This reaction takes place in the 'nucleoplasm' and is mediated by the 'kinase activity' of 'Myt1 kinase'.
			REACT_421 (Reactome)	At the beginning of this reaction, 1 molecule of 'phospho-Retinoblastoma protein', and 1 molecule of 'RNA primer-DNA primer:origin duplex with DNA damage' are present. At the end of this reaction, 1 molecule of 'Rb1:RNA primer-DNA primer:origin duplex with DNA damage' is present. This reaction takes place in the 'nucleus' and is mediated by the 'phosphoprotein phosphatase activity' of 'PP2A'.
			REACT_425 (Reactome)	Follow their formation, the Cyclin E:Cdk2 complexes are translocated to the nucleus.
			REACT_541 (Reactome)	MCM10 is required for human DNA replication. In S. cerevisiae, Mcm10, like Mcm2-7, is required for minichromosome maintenance, but Mcm10 has no sequence homology with these other proteins (Merchant et al., 1997). Genetic studies have demonstrated that Mcm10 is required for DNA replication in S. pombe (Aves et al., 1998) and S. cerevisiae cells (Homesley et al., 2000) and immunodepletion of XlMcm10 interferes with DNA replication in Xenopus egg extracts (Wohlschlegel et al., 2002). Human Mcm10 interacts with chromatin in G1 phase and then dissociates during G2 phase. In S. cerevisiae, Mcm10 has been shown to localize to origins during G1 (Ricke and Bielinsky, 2004), and it may stabilize the association of Mcm2-7 with the pre-replicative complex (Sawyer et al., 2004). This timing of association is consistent with studies that demonstrate that, in Xenopus egg extracts, Mcm10 is required for association of Cdc45, but not Mcm2-7 with chromatin. Biochemical evidence that Mcm10 plays a direct role in the activation of the pre-replicative complex includes the requirement for SpMcm10 in the phosphorylation of the Mcm2-7 complex by DDK (Lee et al., 2004) and the fact that SpMcm10 binds and stimulates DNA polymerase alpha activity (Fien et al., 2004).
			REACT_555 (Reactome)	This event is inferred from the fission yeast. Cyclin B activity is thought to inhibit pre-RC formation by first associating with ORC during DNA replication.
			REACT_592 (Reactome)	Cdc25A dephosphorylates Cdk2 and activates cyclin E-Cdk2 and cyclin A-Cdk2 kinases (Blomberg and Hoffmann, 1999).
			REACT_713 (Reactome)	Cyclin D:CDK4/6 complexes translocate to the nucleus from the cytoplasm, and this nuclear accumulation is directed by p21/p27 (LaBaer et al. 1997).
			REACT_773 (Reactome)	Wee1 phosphorylates Cdk2, inhibiting entry into S-phase (Watanabe et al., 1995; Wu et al., 2001).
			REACT_789 (Reactome)	After pre-RC assembly and Cdc45 association with the origin of replication, Replication Protein A (RPA) also associates with chromatin. RPA is a heterotrimeric complex containing p70, p34, and p11 subunits, and also is required for DNA recombination and DNA repair. The p70 subunit of RPA binds to the primase subunits of Pol alpha:primase. The p70 and p34 subunits of RPA are phosphorylated in a cell cycle-dependent manner. RPA is a single-strand DNA (ssDNA) binding protein and its association with chromatin at this stage suggests that DNA is partially unwound. This suggestion has been confirmed by detection of ssDNA in budding yeast origins of replication using chemical methods.
			REACT_7947 (Reactome)	Prior to mitogen activation, the inhibitory proteins, INK4 (p15, p16, p18, and p19) associate with the catalytic domain of free CDK4/6, preventing its association with cyclins, and thus its activation.
			REACT_8993 (Reactome)	Cyclin E forms a complex with cdk2 and collaborates with the cyclin D-dependent kinases in phosphorylating Rb.
			REACT_8998 (Reactome)	The interaction between the Skp2 subunit of the SCF(Skp2) complex and p27 is dependent upon Cdk2:Cyclin A/E mediated phosphorylation of p27 at Thr 187 (Carrano et al, 1999; Tsvetkov et al, 1999). There is evidence that Cyclin A/B:Cdk1 can also bind and phosphorylate p27 on Thr 187 (Nakayama et al., 2004). This phosphorylation is also essential for the subsequent ubiquitination of p27.
			REACT_9013 (Reactome)	The Myc/Max heterodimer binds to elements in the cdc25A gene and activates transcription in mid to late G1.
			REACT_9017 (Reactome)	The accessory protein, Cks1 promotes efficient interaction between phosphorylated p27 and the SCF (Skp2) complex (Ganoth et al., 2001; Spruck et al., 2001). Cks1 binds to Skp2 in the leucine-rich repeat (LRR) domain and C-terminal tail (Hao et al., 2005). The phosphorylated Thr187 side chain of p27 associates with a phosphate binding site on Cks1, and the side chain containing Glu185 is positioned in the interface between Skp2 and Cks1 where it interacts with both (Hao et al., 2005).
			REACT_9026 (Reactome)	Once in tight contact with the SCF (Skp2):Cks1 complex, phosphorylated p27/p21 is ubiquitinated.
			REACT_9034 (Reactome)	Following ubiquitination by the SCF(Skp2):Cks1 complex, phospho-p27/p21 is degraded by the 26S proteasome.
			REACT_9043 (Reactome)	p27 translocates to the nucleoplasm where it associates with CyclinE:Cdk2 complexes. Localization of p27 to the nucleus is necessary to inhibit Cdk activation by Cdk-activating kinase.
			REACT_9050 (Reactome)	pRB contains, in its C terminus, a cyclin-cdk interaction motif like that found in E2F1 and p21 that enables it to be recognized and phosphorylated by cyclin-cdk complexes.
			REACT_9060 (Reactome)	The association of Cks1 with both Skp2 and phosphorylated p27 promotes a tight interaction between p27 and the SCF complex (Hao et al., 2005).
			REACT_9067 (Reactome)	Phosphorylation of cyclin-dependent kinases (CDKs) by the CDK-activating kinase (CAK) is required for the activation of the CDK kinase activity. The association of p21/p27 with the Cyclin A/E:Cdk2 complex prevents CAK mediated phosphorylation of Cdk2 (Aprelikova et al., 1995).
			REACT_9068 (Reactome)	p21 associates with and inhibits Cyclin:Cdk complexes in the nucleus.
			REACT_907 (Reactome)	At the beginning of this reaction, 1 molecule of 'Mcm2-7 complex', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'phosphorylated Mcm2-7 complex', and 1 molecule of 'ADP' are present. This reaction takes place in the 'nucleus' and is mediated by the 'kinase activity' of 'DDK'.
			REACT_929 (Reactome)	DNA polymerase alpha:primase is comprised of four subunits, p180, p70, p58, and p49. The two primase subunits, p58 and p49, form a tight complex. The p49 subunit contains the DNA primase activity and one role of p58 appears to be tethering p49 to p180, the DNA polymerase catalytic subunit. The fourth subunit, p70, binds p180 and may tether the DNA polymerase alpha:primase complex to Cdc45.
			REACT_951 (Reactome)	At the beginning of this reaction, 1 molecule of 'Mcm10:pre-replicative complex' is present. At the end of this reaction, 1 molecule of 'Mcm10:active pre-replicative complex', and 1 molecule of 'CDT1' are present. This reaction takes place in the 'nucleus'.
			REACT_96 (Reactome)	Phosphorylation of CDK4 on Thr172 depends on prior D-type cyclin binding (Bockstaele et al., 2006).
	RNA primer-DNA primer origin duplex with DNA damage	Arrow	REACT_1408 (Reactome)
RNA primer-DNA primer origin duplex with DNA damage			REACT_421 (Reactome)
RPA Cdc45 CDK DDK Mcm10 pre-replicative complex		Arrow	REACT_1344 (Reactome)
RPA Cdc45 CDK DDK Mcm10 pre-replicative complex		Arrow	REACT_929 (Reactome)
Rb-E2F1/2/3 DP-1 complex			REACT_1882 (Reactome)
Rb1 RNA primer-DNA primer origin duplex with DNA damage			REACT_1277 (Reactome)
	SCF	Arrow	REACT_111089 (Reactome)
	SCF	Arrow	REACT_9034 (Reactome)
SCF			REACT_111194 (Reactome)
SCF			REACT_9017 (Reactome)
SCF			REACT_9060 (Reactome)
	TOP2A	Arrow	REACT_111167 (Reactome)
	Ub-p-T401,S672,1035-RBL2	Arrow	REACT_111089 (Reactome)
WEE1		mim-catalysis	REACT_773 (Reactome)
origin of replication			REACT_1344 (Reactome)
	p-MuvB complex	Arrow	REACT_111075 (Reactome)
p-MuvB complex			REACT_111236 (Reactome)
	p-S795-RB1	Arrow	REACT_1882 (Reactome)
p-S795-RB1			REACT_421 (Reactome)
	p-T369,S640,S964,S975-RBL1	Arrow	REACT_111248 (Reactome)
p-T369,S640,S964,S975-RBL1			REACT_111148 (Reactome)
p-T401,S672,1035-RBL2 SCF			REACT_111089 (Reactome)
p-T401,S672,1035-RBL2 SCF		mim-catalysis	REACT_111089 (Reactome)
	p-T401,S672,S1035-RBL2	Arrow	REACT_111206 (Reactome)
p-T401,S672,S1035-RBL2			REACT_111170 (Reactome)
p-T401,S672,S1035-RBL2			REACT_111194 (Reactome)
p21/p27			REACT_2081 (Reactome)
p21/p27			REACT_334 (Reactome)
p21/p27		mim-catalysis	REACT_334 (Reactome)
	phosphorylated Mcm2-7 complex	Arrow	REACT_907 (Reactome)
pre-replicative complex			REACT_541 (Reactome)
	ubiquitin	Arrow	REACT_9034 (Reactome)
ubiquitin			REACT_111089 (Reactome)
ubiquitin			REACT_9026 (Reactome)