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

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1153, 20, 57, 633010, 46, 569, 364453, 587, 27, 50, 5251, 59613055351626, 283431343535315451642059445, 172237, 46, 572926, 40, 419, 30, 3637, 57135512, 45193222202, 496354, 8, 14, 21, 23...TFDP1, TFDP2 RNA primerorigin duplexDNA polymerase alphaprimase complex CDC6ORCorigin complex Cyclin ECdk2 complexes Orc2 associated with MCM8 Cdk4/6 Cyclin B Cyclin Dphospho-CDK4/6p21/p27 E2F4/5 E2F4TFDP1,TFDP2 p21/p27 RNA primer-DNA primerorigin duplex CDC6ORCorigin complex RNA primer-DNA primerorigin duplex with DNA damage RBL1E2F4TFDP1,TFDP2 DNA polymerase alphaprimaseDNA polymerase alphaorigin complex TFDP1, TFDP2 Cyclin E Orc2 associated with MCM8 CAK Mcm10active pre-replicative complex Cyclin E/A Cyclin ECdk2 complex p21/p27 Mcm2-7 complex Rb1RNA primer-DNA primerorigin duplex with DNA damage p-MuvB complex ubiquitin nucleoplasmDNA Replication Factor A active pre-replicative complex ORCorigin phospho-p27/p21 CDK ORCorigin CDT1CDC6ORCorigin complex DNA polymerase epsilon DDK Mcm2-7 complex Cyclin E/A active pre-replicative complex RBL2E2F4/5DP1/2 Cdc45CDKDDKMcm10pre-replicative complex phospho-p27/p21 Cyclin E/ACdk2 Orc2 associated with MCM8 Cyclin E/ACdk2 Mcm10active pre-replicative complex Cyclin EPhosho-Cdk2 CDKDDKMcm10pre-replicative complex HDAC1RBL2E2F4/5DP1/2 DNA polymerase epsilon SCFORCorigin Cyclin E/A SCFCyclin E Cyclin DCdk4/6p21/p27 Cyclin E/ACdk2phospho-p27/p21 CDK p-T401,S672,1035-RBL2SCFRBL1E2F4DP1/2Cyclin E/ACDK2 ubiquitin Orc2 associated with MCM8 DDK active pre-replicative complex active pre-replicative complex DNA polymerase epsilon SCFDNA polymerase epsilonorigin complex SCFCyclin E/ACdk2 Cyclin E2Cdk2 complex Cyclin E/ACdk2p27/p21 complex RBL2E2F4/5DP1/2 Cyclin E RBL1Cyclin E/ACDK2 Cyclin E/ACdk2phospho-p27/p21SCFMcm2-7 complex DREAM complex ORCorigin Cyclin E/A ORCorigin E2F4/5 Cyclin E/ACdk2 Cyclin ECdk2p21/p27 complex RNA primer-DNA primerorigin duplex with DNA damage RBL2E2F4/5DP1/2 Cyclin E/A DNA polymerase epsilonorigin complex RBL2E2F4/5DP1/2 CDC6ORCorigin complex Cyclin EPhosho-Cdk2 DNA polymerase alphaprimase Orc2 associated with MCM8 p21/p27 SCFE2F1/2/3 Rb1RNA primer-DNA primerorigin duplex with DNA damage Cyclin B Mcm10active pre-replicative complex RBL1E2F4TFDP1,TFDP2 DNA polymerase alphaprimase CDC6ORCorigin complex Cyclin EPhospho-Cdk2p21/p27 TFDP1, TFDP2 PP2A Mcm10pre-replicative complex HDAC1RBL1E2F4TFDP1,TFDP2 CDC6ORCorigin complex TFDP1, TFDP2 E2F1TFDP1 Rb-E2F1/2/3DP-1 complex CDKDDKMcm10pre-replicative complex RBL2E2F4/5DP1/2Cyclin E/ACDK2 E2F4/5 Cyclin E1Cdk2 complex TFDP1, TFDP2 Cyclin E/A p21/p27 Cyclin E/ACdk2phospho-p27/p21 Cyclin E/ACdk2phospho-p27/p21SCFE2F4/5DP1/2 Cyclin Ephospho-Cdk2 RBL1E2F4TFDP1,TFDP2 E2F1/2/3 ORCorigin Cyclin ECdk2 complexes pre-replicative complex Cyclin EPhosho-Cdk2 pre-replicative complex Cyclin E/ACdk2 26S proteasome ORCorigincyclin Bcdk1 complex Orc2 associated with MCM8 E2F4/5 Cyclin E SCFCyclin BCdk1 complex DNA polymerase alphaprimase Mcm10active pre-replicative complex Cyclin E/ACdk2 RBL2Cyclin E/ACDK2 Cyclin BCdk1 complex Mcm2-7 complex RBL1E2F4TFDP1,TFDP2 TFDP1, TFDP2 Cyclin E/A Mcm2-7 complex CDC6ORCorigin complex Cyclin E MuvB complex SCFE2F4/5 SCFp-MuvB complex Aborted replication complex DDK PP2A ORCorigin Cyclin Ephospho-Cdk2 Complex SCFINK4A TFDP1, TFDP2 SCFCyclin E1phospho-Cdk2 complex SCFMcm2-7 complex E2F4/5 Cyclin E/ACdk2 Myc/Max heterodimer TFDP1, TFDP2 TFDP1, TFDP2 Orc2 associated with MCM8 Cyclin E/A Cdc45CDKDDKMcm10pre-replicative complex E2F1TFDP1 CDK DDK phosphorylated Mcm2-7 complex CDK Cyclin DCDK4/6p21/p27 complex Cyclin E/ACdk2phospho-p27/p21 Cyclin E/A RNA primer-DNA primerorigin duplex with DNA damage Mcm2-7 complex Cyclin E/ACdk2multiubiquitinated phospho-p27/p21SCFORCorigin TFDP1, TFDP2 CDT1CDC6ORCorigin complex phospho-p27/p21 Mcm2-7 complex CDKDDKMcm10pre-replicative complex cytosolUb-p-T401,S672,1035-RBL2 Cyclin E/ACdk2 RPACdc45CDKDDKMcm10pre-replicative complex Cyclin E/ACdk2 DP-1E2F1/2/3 Cdk4/6INK4A complex Cyclin E2phospho-Cdk2 complex RBL2E2F4/5DP1/2 Orc2 associated with MCM8 DNA Replication Factor A TFDP1, TFDP2 POLA1 ORC4 ORC2 E2F4 E2F5 MCM5 TFDP1 MCM10 CDC7 PP2ACDKN1A PSMC3 RBL1 ORC3 CDK2 Mcm10pre-replicative complexMcm2-7 complexATPPPP2R3B E2F4 RBL2 PSMD11 CDK2 CCNE2 MCM8 TFDP1 E2F4/5DP1/2CCNB1 RBL2Cyclin E/ACDK2PSMD1 PSMB6 CDK2 TFDP2 MCM7 PSMC4 ORC5 SKP1 phosphorylated Mcm2-7 complexDREAM complexORC2 ORC2 TFDP1 ORC3 PRIM2 CDKN2D MCM4 E2F1 ORC4 E2F5 MCM8 MCM3 CDK1CUL1 SKP2 SKP1 ORC5 ATPORC5 TFDP2 RBBP4 PSMD4 WEE1ADPORC2 ATPPOLE2 ATPH2OUBBRPA4 POLE2 PSMB7 ORC3 UBCE2F4 MCM8 LIN9 PSMA2 TFDP1 TFDP1 TFDP2 MCM8 p21/p27RBL1Cyclin EPhospho-Cdk2ATPCyclin E/ACdk2RBL2E2F4/5DP1/2CDC6 ORC4 RBL1 UBBSKP2 HDAC1RBL2E2F4/5DP1/2ORC1 Cdk4/6LIN37 PSMA7 ORC2 MCM7 CDK2 p-T187-CDKN1B ORC1 CDKN1B TFDP2 PKMYT1Cdk4/6INK4A complexMCM8 DP-1E2F1/2/3LIN37 CDC6 POLA2 CDK2 PSMD9 CCNE1 UBCADPTFDP1 MCM5 E2F2 ORC4 POLE2 PSMA3 MCM6 MCM7 p-T160-CDK2 CDC7 p-CDK2 E2F4 Cyclin E/ACdk2multiubiquitinated phospho-p27/p21SCFCCNE1 ADPCDC6 p-T187-CDKN1B MuvB complexCDKN1A MCM2 ORC5 CDKN1A RPA1 MCM8 CUL1 H2OPSME3 LIN54 MCM10 CAKTFDP1 RBL1PSMB2 POLE DNA polymerase epsilonCCNE2 ORC6 RBL2E2F4/5DP1/2LIN52 MCM6 CDK2 PiPOLE p-T401,S672,S1035-RBL2 E2F1TFDP1CCNE2 E2F4 Aborted replication complexCDKN2B UBBRB1 PiSKP1 CDKN1B ADPMCM2 RBL2 E2F4 RPA3 TFDP1 CUL1 CDC7 SKP1 MCM4 RPS27ACyclin D26S proteasomep-T369,S640,S964,S975-RBL1PCNAORCoriginCDKN1B MCM3 CDC6CDC7 MCM4 LIN9 E2F1 ORC6 p-S28-LIN52 PSMD12 E2F4TFDP1,TFDP2CDKDDKMcm10pre-replicative complexORC6 CKS1B p-S28-LIN52 ADPCDC25ACDK2 PSMB3 p16-INK4a PRIM1 ORC1 MCM2 DDKCyclin ECdk2 complexMCM2 ORC2 ORC1 ADPORCorigincyclin Bcdk1 complexADPLIN54 RBL1 CCNH Cyclin Dphospho-CDK4/6p21/p27ubiquitinORC3 SCFp-MuvB complexE2F1 DNA polymerase alphaprimaseCDK2 ORC6 LIN54 Rb-E2F1/2/3DP-1 complexPSMA5 TFDP1 MYC RBL1Cyclin E/ACDK2RBL1E2F4DP1/2Cyclin E/ACDK2p-RB1 UBCCUL1 ORC2 TFDP1 PSMA4 TOP2APSMC5 DYRK1Ap-S130-CDKN1A ORC3 CDC45 E2F1p-S795-RB1CDKN1B HDAC1RBL1E2F4TFDP1,TFDP2RBL1E2F4TFDP1,TFDP2CKS1BADPp-CDK2 MCM6 MCM3 ORC4 CDC6 Cyclin Ephospho-Cdk2 TFDP2 ORC4 CDK2 RBL1 E2F5 UBCRBBP4 UBCH2OPSMD14 LIN9 CDK1 CCNE1 Cdk4/6HDAC1 ATPRB1CDKN1B PSMB4 CCNE2 UBCUb-p-T401,S672,1035-RBL2ORC2 CCNE1 TFDP1 CDK2ADPUBBPSMD13 ATPCDK2 CDK2 MCM3 CDK2 ORC1 PSMC6 SKP2 RPA1 p-S130-CDKN1A p-T401,S672,S1035-RBL2 Cyclin EDBF4 UBCCDC45 E2F4 MCM8 CDT1 MCM6 UBBMCM10 RB1 Cyclin DCDK4/6p21/p27 complexp-T187-CDKN1B CDC6 CCNE2 PP2AMCM10 ORC5 RNA primer-DNA primerorigin duplex with DNA damagePSMC2 CDK2 LIN37 Cyclin DCdk4/6p21/p27RBL2 MCM4 SKP1 PSMD5 MCM6 HDAC1 CCNE2 DNA polymerase epsilonorigin complexMCM2 MCM2 ORC5 ATPubiquitinCDKN2C E2F4 PRIM2 MCM4 ORC6 Cyclin E/ACdk2phospho-p27/p21MCM2 CDK1 MCM5 MCM3 CDKCyclin Ephospho-Cdk2 ComplexSKP2 RBL1E2F4TFDP1,TFDP2CDKN1BCKS1B ORC3 Cyclin E2Cdk2 complexPSMB10 RBL2PSME1 UBCPSMD10 MCM3 UBCDBF4 Cyclin E/ACdk2phospho-p27/p21SCFTFDP1 PSMA6 MNAT1 ORC6 PSME2 ATPCyclin EPhosho-Cdk2 E2F3 PSMF1 CDK2 MCM3 RB1 UBBTFDP2 RBL2INK4ACyclin BCdk1 complexRPA3 CCNE1 CDK2 PSMD8 POLA2 SKP1 ORC4 Cdc45CDKDDKMcm10pre-replicative complexCKS1B Cyclin E1Cdk2 complexE2F3 PRIM1 CDK2 ORC4 UBCMCM7 UBCPSMB9 CDKN1BRBL2 MCM4 ADPTFDP2 E2F5 UBCRNA primer-DNA primerorigin duplexORC3 p21/p27ORC1 PRIM1 ORC1 TFDP2 p-T160-CDK2 ORC3 MCM5 CDKN1ARBL1 CDT1 p-S130-CDKN1A PSMD3 TFDP2 MCM7 CDK7 SCFRBL2E2F4/5DP1/2Cyclin E/ACDK2ATPCCNE2 CDT1Cyclin ECdk2p21/p27 complexCCNE1 ORC5 PSMD6 E2F2 UBCMCM3 ORC5 TFDP2 PSMD2 ADPPOLE p-CDK2 PRIM2 Mcm10active pre-replicative complexPOLA1 E2F5 Cyclin E1phospho-Cdk2 complexCDKN1A MAX CDK6 UBA52RPACdc45CDKDDKMcm10pre-replicative complexRPA2 PSMB5 PiMCM7 TFDP2 MCM10 DNA polymerase alphaprimaseDNA polymerase alphaorigin complexUBCATPMCM8 MCM6 RPA4 RBBP4 CCNB1 ADPCDK2 DNA Replication Factor AMCM7 Cyclin ECdk2 complexesCDKN1AMCM6 TFDP1 CDK2 PSMA1 PSMB1 MCM5 ORC6 RB1 ATPSCFUBCTFDP1 PSMB8 UBCCyclin E2phospho-Cdk2 complexUBCCDC45p-T160-CDK2 DBF4 MCM5 MCM4 PSMC1 CDK4 ATPCDKN1A E2F1 targetsMCM5 CDC25APSMD7 CUL1 MCM10MYBL2RBL1RPS27AORC6 E2F4 E2F5 MCM4 E2F4 POLA1 Myc/Max heterodimerRBL2 CDC6 UBA52Rb1RNA primer-DNA primerorigin duplex with DNA damagePi CCNAp-T401,S672,1035-RBL2SCFHDAC1RBL2 UBCMCM7 E2F4 MCM6 SKP2 p-T401,S672,S1035-RBL2SKP2 CCNE1 CKS1B ORC1 MCM2 POLA2 MCM5 ADPpre-replicative complexRPA2 Cyclin E/ACdk2p27/p21 complexorigin of replicationCKS1B DBF4 CUL1 E2F1 E2F1TFDP1 1118, 424339483512, 45


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  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

View all...
CompareRevisionActionTimeUserComment
114646view16:11, 25 January 2021ReactomeTeamReactome version 75
113094view11:15, 2 November 2020ReactomeTeamReactome version 74
112328view15:25, 9 October 2020ReactomeTeamReactome version 73
112225view14:39, 2 October 2020DeSlOntology Term : 'M/G1 transition pathway' added !
101227view11:12, 1 November 2018ReactomeTeamreactome version 66
100765view20:38, 31 October 2018ReactomeTeamreactome version 65
100309view19:15, 31 October 2018ReactomeTeamreactome version 64
99855view15:59, 31 October 2018ReactomeTeamreactome version 63
99413view14:35, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93757view13:34, 16 August 2017ReactomeTeamreactome version 61
93279view11:19, 9 August 2017ReactomeTeamreactome version 61
86357view09:16, 11 July 2016ReactomeTeamreactome version 56
83315view10:46, 18 November 2015ReactomeTeamVersion54
81454view12:59, 21 August 2015ReactomeTeamVersion53
76928view08:20, 17 July 2014ReactomeTeamFixed remaining interactions
76633view12:00, 16 July 2014ReactomeTeamFixed remaining interactions
76130view12:48, 11 June 2014Anwesha
76129view12:44, 11 June 2014ReactomeTeamAdding missing reactome URL
75666view10:57, 10 June 2014ReactomeTeamReactome 48 Update
75021view13:53, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74665view08:43, 30 April 2014ReactomeTeamReactome46
68884view17:26, 8 July 2013MaintBotUpdated to 2013 gpml schema
44912view10:35, 6 October 2011MartijnVanIerselOntology Term : 'cell cycle pathway, mitotic' added !
42076view21:55, 4 March 2011MaintBotAutomatic update
39884view05:54, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasomeComplexREACT_7467 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Aborted replication complexComplexREACT_2817 (Reactome)
CAKComplexREACT_5717 (Reactome)
CCNAProteinREACT_5498 (Reactome)
CCNB1 ProteinP14635 (Uniprot-TrEMBL)
CCNE1 ProteinP24864 (Uniprot-TrEMBL)
CCNE2 ProteinO96020 (Uniprot-TrEMBL)
CCNH ProteinP51946 (Uniprot-TrEMBL)
CDC25AProteinP30304 (Uniprot-TrEMBL)
CDC45 ProteinO75419 (Uniprot-TrEMBL)
CDC45ProteinO75419 (Uniprot-TrEMBL)
CDC6 ProteinQ99741 (Uniprot-TrEMBL)
CDC6ProteinQ99741 (Uniprot-TrEMBL)
CDC7 ProteinO00311 (Uniprot-TrEMBL)
CDK

DDK Mcm10

pre-replicative complex
ComplexREACT_2458 (Reactome)
CDK1 ProteinP06493 (Uniprot-TrEMBL)
CDK1ProteinP06493 (Uniprot-TrEMBL)
CDK2 ProteinP24941 (Uniprot-TrEMBL)
CDK2ProteinP24941 (Uniprot-TrEMBL)
CDK4 ProteinP11802 (Uniprot-TrEMBL)
CDK6 ProteinQ00534 (Uniprot-TrEMBL)
CDK7 ProteinP50613 (Uniprot-TrEMBL)
CDKN1A ProteinP38936 (Uniprot-TrEMBL)
CDKN1AProteinP38936 (Uniprot-TrEMBL)
CDKN1B ProteinP46527 (Uniprot-TrEMBL)
CDKN1BProteinP46527 (Uniprot-TrEMBL)
CDKN2B ProteinP42772 (Uniprot-TrEMBL)
CDKN2C ProteinP42773 (Uniprot-TrEMBL)
CDKN2D ProteinP55273 (Uniprot-TrEMBL)
CDKComplexREACT_5476 (Reactome)
CDT1 ProteinQ9H211 (Uniprot-TrEMBL)
CDT1ProteinQ9H211 (Uniprot-TrEMBL)
CKS1B ProteinP61024 (Uniprot-TrEMBL)
CKS1BProteinP61024 (Uniprot-TrEMBL)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
Cdc45

CDK DDK Mcm10

pre-replicative complex
ComplexREACT_4546 (Reactome)
Cdk4/6 INK4A complexComplexREACT_8076 (Reactome)
Cdk4/6REACT_4552 (Reactome)
Cdk4/6ProteinREACT_8720 (Reactome)
Cyclin B Cdk1 complexComplexREACT_4583 (Reactome)
Cyclin D

CDK4/6

p21/p27 complex
ComplexREACT_2341 (Reactome)
Cyclin D

Cdk4/6

p21/p27
ComplexREACT_2453 (Reactome)
Cyclin D

phospho-CDK4/6

p21/p27
ComplexREACT_3625 (Reactome)
Cyclin DProteinREACT_8063 (Reactome)
Cyclin E

Cdk2

p21/p27 complex
ComplexREACT_3804 (Reactome)
Cyclin E Cdk2 complexComplexREACT_3296 (Reactome)
Cyclin E Cdk2 complexesComplexREACT_5247 (Reactome)
Cyclin E Phosho-Cdk2 ComplexREACT_9167 (Reactome)
Cyclin E Phospho-Cdk2ComplexREACT_9136 (Reactome)
Cyclin E phospho-Cdk2 ComplexComplexREACT_4112 (Reactome)
Cyclin E phospho-Cdk2 ComplexREACT_9190 (Reactome)
Cyclin E/A

Cdk2 multiubiquitinated phospho-p27/p21

SCF
ComplexREACT_9266 (Reactome)
Cyclin E/A

Cdk2

p27/p21 complex
ComplexREACT_9314 (Reactome)
Cyclin E/A

Cdk2 phospho-p27/p21

SCF
ComplexREACT_9193 (Reactome)
Cyclin E/A

Cdk2

phospho-p27/p21
ComplexREACT_9321 (Reactome)
Cyclin E/A Cdk2ComplexREACT_9091 (Reactome)
Cyclin E1 Cdk2 complexComplexREACT_4601 (Reactome)
Cyclin E1 phospho-Cdk2 complexComplexREACT_2714 (Reactome)
Cyclin E2 Cdk2 complexComplexREACT_5296 (Reactome)
Cyclin E2 phospho-Cdk2 complexComplexREACT_3967 (Reactome)
Cyclin EProteinREACT_5284 (Reactome)
DBF4 ProteinQ9UBU7 (Uniprot-TrEMBL)
DDKComplexREACT_4813 (Reactome)
DNA Replication Factor AComplexREACT_5149 (Reactome)
DNA polymerase alpha

primase DNA polymerase alpha

origin complex
ComplexREACT_3167 (Reactome)
DNA polymerase alpha primaseComplexREACT_3725 (Reactome)
DNA polymerase epsilon origin complexComplexREACT_3283 (Reactome)
DNA polymerase epsilonComplexREACT_4621 (Reactome)
DP-1 E2F1/2/3ComplexREACT_76628 (Reactome)
DREAM complexComplexREACT_111426 (Reactome)
DYRK1AProteinQ13627 (Uniprot-TrEMBL)
E2F1 TFDP1ComplexREACT_5400 (Reactome)
E2F1 ProteinQ01094 (Uniprot-TrEMBL)
E2F1 targetsProteinREACT_22550 (Reactome)
E2F1ProteinQ01094 (Uniprot-TrEMBL)
E2F2 ProteinQ14209 (Uniprot-TrEMBL)
E2F3 ProteinO00716 (Uniprot-TrEMBL)
E2F4 TFDP1,TFDP2ComplexREACT_111631 (Reactome)
E2F4 ProteinQ16254 (Uniprot-TrEMBL)
E2F4/5 DP1/2ComplexREACT_111584 (Reactome)
E2F5 ProteinQ15329 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
HDAC1

RBL1 E2F4

TFDP1,TFDP2
ComplexREACT_111485 (Reactome)
HDAC1

RBL2 E2F4/5

DP1/2
ComplexREACT_111840 (Reactome)
HDAC1 ProteinQ13547 (Uniprot-TrEMBL)
HDAC1ProteinQ13547 (Uniprot-TrEMBL)
INK4AREACT_8915 (Reactome)
LIN37 ProteinQ96GY3 (Uniprot-TrEMBL)
LIN52 ProteinQ52LA3 (Uniprot-TrEMBL)
LIN54 ProteinQ6MZP7 (Uniprot-TrEMBL)
LIN9 ProteinQ5TKA1 (Uniprot-TrEMBL)
MAX ProteinP61244 (Uniprot-TrEMBL)
MCM10 ProteinQ7L590 (Uniprot-TrEMBL)
MCM10ProteinQ7L590 (Uniprot-TrEMBL)
MCM2 ProteinP49736 (Uniprot-TrEMBL)
MCM3 ProteinP25205 (Uniprot-TrEMBL)
MCM4 ProteinP33991 (Uniprot-TrEMBL)
MCM5 ProteinP33992 (Uniprot-TrEMBL)
MCM6 ProteinQ14566 (Uniprot-TrEMBL)
MCM7 ProteinP33993 (Uniprot-TrEMBL)
MCM8 ProteinQ9UJA3 (Uniprot-TrEMBL)
MNAT1 ProteinP51948 (Uniprot-TrEMBL)
MYBL2ProteinP10244 (Uniprot-TrEMBL)
MYC ProteinP01106 (Uniprot-TrEMBL)
Mcm10 active pre-replicative complexComplexREACT_2683 (Reactome)
Mcm10 pre-replicative complexComplexREACT_5685 (Reactome)
Mcm2-7 complexComplexREACT_4763 (Reactome)
MuvB complexComplexREACT_111706 (Reactome)
Myc/Max heterodimerComplexREACT_9233 (Reactome)
ORC

origin cyclin B

cdk1 complex
ComplexREACT_4235 (Reactome)
ORC originComplexREACT_3844 (Reactome)
ORC1 ProteinQ13415 (Uniprot-TrEMBL)
ORC2 ProteinQ13416 (Uniprot-TrEMBL)
ORC3 ProteinQ9UBD5 (Uniprot-TrEMBL)
ORC4 ProteinO43929 (Uniprot-TrEMBL)
ORC5 ProteinO43913 (Uniprot-TrEMBL)
ORC6 ProteinQ9Y5N6 (Uniprot-TrEMBL)
PCNAProteinP12004 (Uniprot-TrEMBL)
PKMYT1ProteinQ99640 (Uniprot-TrEMBL)
POLA1 ProteinP09884 (Uniprot-TrEMBL)
POLA2 ProteinQ14181 (Uniprot-TrEMBL)
POLE ProteinQ07864 (Uniprot-TrEMBL)
POLE2 ProteinP56282 (Uniprot-TrEMBL)
PP2AComplexREACT_111616 (Reactome)
PP2AComplexREACT_111771 (Reactome)
PPP2R3B ProteinQ9Y5P8 (Uniprot-TrEMBL)
PRIM1 ProteinP49642 (Uniprot-TrEMBL)
PRIM2 ProteinP49643 (Uniprot-TrEMBL)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7 ProteinO14818 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB2 ProteinP49721 (Uniprot-TrEMBL)
PSMB3 ProteinP49720 (Uniprot-TrEMBL)
PSMB4 ProteinP28070 (Uniprot-TrEMBL)
PSMB5 ProteinP28074 (Uniprot-TrEMBL)
PSMB6 ProteinP28072 (Uniprot-TrEMBL)
PSMB7 ProteinQ99436 (Uniprot-TrEMBL)
PSMB8 ProteinP28062 (Uniprot-TrEMBL)
PSMB9 ProteinP28065 (Uniprot-TrEMBL)
PSMC1 ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6 ProteinP62333 (Uniprot-TrEMBL)
PSMD1 ProteinQ99460 (Uniprot-TrEMBL)
PSMD10 ProteinO75832 (Uniprot-TrEMBL)
PSMD11 ProteinO00231 (Uniprot-TrEMBL)
PSMD12 ProteinO00232 (Uniprot-TrEMBL)
PSMD13 ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD14 ProteinO00487 (Uniprot-TrEMBL)
PSMD2 ProteinQ13200 (Uniprot-TrEMBL)
PSMD3 ProteinO43242 (Uniprot-TrEMBL)
PSMD4 ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6 ProteinQ15008 (Uniprot-TrEMBL)
PSMD7 ProteinP51665 (Uniprot-TrEMBL)
PSMD8 ProteinP48556 (Uniprot-TrEMBL)
PSMD9 ProteinO00233 (Uniprot-TrEMBL)
PSME1 ProteinQ06323 (Uniprot-TrEMBL)
PSME2 ProteinQ9UL46 (Uniprot-TrEMBL)
PSME3 ProteinP61289 (Uniprot-TrEMBL)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
Pi MetaboliteCHEBI:18367 (ChEBI)
PiMetaboliteCHEBI:18367 (ChEBI)
RB1 ProteinP06400 (Uniprot-TrEMBL)
RB1ProteinP06400 (Uniprot-TrEMBL)
RBBP4 ProteinQ09028 (Uniprot-TrEMBL)
RBL1

Cyclin E/A

CDK2
ComplexREACT_111400 (Reactome)
RBL1

E2F4 DP1/2 Cyclin E/A

CDK2
ComplexREACT_111813 (Reactome)
RBL1

E2F4

TFDP1,TFDP2
ComplexREACT_111376 (Reactome)
RBL1 ProteinP28749 (Uniprot-TrEMBL)
RBL1ProteinP28749 (Uniprot-TrEMBL)
RBL2

Cyclin E/A

CDK2
ComplexREACT_111575 (Reactome)
RBL2

E2F4/5 DP1/2 Cyclin E/A

CDK2
ComplexREACT_111339 (Reactome)
RBL2

E2F4/5

DP1/2
ComplexREACT_111674 (Reactome)
RBL2 ProteinQ08999 (Uniprot-TrEMBL)
RBL2ProteinQ08999 (Uniprot-TrEMBL)
RNA primer-DNA primer origin duplex with DNA damageComplexREACT_2843 (Reactome)
RNA primer-DNA primer origin duplexComplexREACT_5497 (Reactome)
RPA

Cdc45 CDK DDK Mcm10

pre-replicative complex
ComplexREACT_2568 (Reactome)
RPA1 ProteinP27694 (Uniprot-TrEMBL)
RPA2 ProteinP15927 (Uniprot-TrEMBL)
RPA3 ProteinP35244 (Uniprot-TrEMBL)
RPA4 ProteinQ13156 (Uniprot-TrEMBL)
RPS27AProteinP62979 (Uniprot-TrEMBL)
Rb-E2F1/2/3 DP-1 complexComplexREACT_4483 (Reactome)
Rb1

RNA primer-DNA primer

origin duplex with DNA damage
ComplexREACT_3869 (Reactome)
SCFComplexREACT_9182 (Reactome)
SCFComplexREACT_9339 (Reactome)
SKP1 ProteinP63208 (Uniprot-TrEMBL)
SKP2 ProteinQ13309 (Uniprot-TrEMBL)
TFDP1 ProteinQ14186 (Uniprot-TrEMBL)
TFDP2 ProteinQ14188 (Uniprot-TrEMBL)
TOP2AProteinP11388 (Uniprot-TrEMBL)
UBA52ProteinP62987 (Uniprot-TrEMBL)
UBBProteinP0CG47 (Uniprot-TrEMBL)
UBCProteinP0CG48 (Uniprot-TrEMBL)
Ub-p-T401,S672,1035-RBL2ComplexREACT_111808 (Reactome)
WEE1ProteinP30291 (Uniprot-TrEMBL)
origin of replicationREACT_3087 (Reactome)
p-CDK2 ProteinP24941 (Uniprot-TrEMBL)
p-MuvB complexComplexREACT_111785 (Reactome)
p-RB1 ProteinP06400 (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 ProteinP38936 (Uniprot-TrEMBL)
p-S28-LIN52 ProteinQ52LA3 (Uniprot-TrEMBL)
p-S795-RB1ProteinP06400 (Uniprot-TrEMBL)
p-T160-CDK2 ProteinP24941 (Uniprot-TrEMBL)
p-T187-CDKN1B ProteinP46527 (Uniprot-TrEMBL)
p-T369,S640,S964,S975-RBL1ProteinP28749 (Uniprot-TrEMBL)
p-T401,S672,1035-RBL2 SCFComplexREACT_111614 (Reactome)
p-T401,S672,S1035-RBL2 ProteinQ08999 (Uniprot-TrEMBL)
p-T401,S672,S1035-RBL2ProteinQ08999 (Uniprot-TrEMBL)
p16-INK4a ProteinP42771 (Uniprot-TrEMBL)
p21/p27ProteinREACT_8233 (Reactome)
p21/p27ProteinREACT_8306 (Reactome)
phosphorylated Mcm2-7 complexComplexREACT_4259 (Reactome)
pre-replicative complexComplexREACT_4388 (Reactome)
ubiquitinProteinREACT_3995 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisREACT_9034 (Reactome)
ADPArrowREACT_111075 (Reactome)
ADPArrowREACT_111206 (Reactome)
ADPArrowREACT_111248 (Reactome)
ADPArrowREACT_1657 (Reactome)
ADPArrowREACT_1882 (Reactome)
ADPArrowREACT_2081 (Reactome)
ADPArrowREACT_384 (Reactome)
ADPArrowREACT_773 (Reactome)
ADPArrowREACT_8993 (Reactome)
ADPArrowREACT_8998 (Reactome)
ADPArrowREACT_9067 (Reactome)
ADPArrowREACT_907 (Reactome)
ADPArrowREACT_96 (Reactome)
ATPREACT_111075 (Reactome)
ATPREACT_111206 (Reactome)
ATPREACT_111248 (Reactome)
ATPREACT_1657 (Reactome)
ATPREACT_1882 (Reactome)
ATPREACT_2081 (Reactome)
ATPREACT_384 (Reactome)
ATPREACT_773 (Reactome)
ATPREACT_8993 (Reactome)
ATPREACT_8998 (Reactome)
ATPREACT_9067 (Reactome)
ATPREACT_907 (Reactome)
ATPREACT_96 (Reactome)
CAKmim-catalysisREACT_9067 (Reactome)
CAKmim-catalysisREACT_96 (Reactome)
CCNAArrowREACT_111173 (Reactome)
CDC25AArrowREACT_111167 (Reactome)
CDC25AArrowREACT_1205 (Reactome)
CDC25Amim-catalysisREACT_592 (Reactome)
CDC45REACT_135 (Reactome)
CDC6ArrowREACT_111167 (Reactome)
CDK

DDK Mcm10

pre-replicative complex
REACT_135 (Reactome)
CDK1ArrowREACT_111173 (Reactome)
CDK2REACT_1683 (Reactome)
CDKREACT_2227 (Reactome)
CDT1ArrowREACT_951 (Reactome)
CKS1BREACT_9017 (Reactome)
Cdc45

CDK DDK Mcm10

pre-replicative complex
REACT_789 (Reactome)
Cdk4/6 INK4A complexTBarREACT_2081 (Reactome)
Cdk4/6REACT_2081 (Reactome)
Cdk4/6REACT_7947 (Reactome)
Cyclin B Cdk1 complexArrowREACT_1205 (Reactome)
Cyclin B Cdk1 complexREACT_555 (Reactome)
Cyclin D

CDK4/6

p21/p27 complex
ArrowREACT_2081 (Reactome)
Cyclin D

Cdk4/6

p21/p27
REACT_96 (Reactome)
Cyclin D

phospho-CDK4/6

p21/p27
ArrowREACT_96 (Reactome)
Cyclin D

phospho-CDK4/6

p21/p27
mim-catalysisREACT_111206 (Reactome)
Cyclin D

phospho-CDK4/6

p21/p27
mim-catalysisREACT_111248 (Reactome)
Cyclin D

phospho-CDK4/6

p21/p27
mim-catalysisREACT_1882 (Reactome)
Cyclin DREACT_2081 (Reactome)
Cyclin E Cdk2 complexesArrowREACT_592 (Reactome)
Cyclin E Cdk2 complexesREACT_334 (Reactome)
Cyclin E Cdk2 complexesREACT_773 (Reactome)
Cyclin E Cdk2 complexesREACT_9067 (Reactome)
Cyclin E Phosho-Cdk2 ArrowREACT_9067 (Reactome)
Cyclin E Phosho-Cdk2 REACT_9050 (Reactome)
Cyclin E Phospho-Cdk2REACT_8993 (Reactome)
Cyclin E Phospho-Cdk2mim-catalysisREACT_8993 (Reactome)
Cyclin E phospho-Cdk2 ArrowREACT_8993 (Reactome)
Cyclin E phospho-Cdk2 ComplexArrowREACT_773 (Reactome)
Cyclin E phospho-Cdk2 ComplexREACT_592 (Reactome)
Cyclin E/A

Cdk2 multiubiquitinated phospho-p27/p21

SCF
mim-catalysisREACT_9026 (Reactome)
Cyclin E/A

Cdk2

p27/p21 complex
REACT_8998 (Reactome)
Cyclin E/A

Cdk2

p27/p21 complex
mim-catalysisREACT_8998 (Reactome)
Cyclin E/A

Cdk2 phospho-p27/p21

SCF
REACT_9026 (Reactome)
Cyclin E/A

Cdk2

phospho-p27/p21
ArrowREACT_8998 (Reactome)
Cyclin E/A

Cdk2

phospho-p27/p21
REACT_9060 (Reactome)
Cyclin E/A Cdk2ArrowREACT_9034 (Reactome)
Cyclin E/A Cdk2REACT_111039 (Reactome)
Cyclin E/A Cdk2REACT_111079 (Reactome)
Cyclin E/A Cdk2REACT_111109 (Reactome)
Cyclin E/A Cdk2REACT_111202 (Reactome)
Cyclin E1 Cdk2 complexREACT_1657 (Reactome)
Cyclin E1 phospho-Cdk2 complexArrowREACT_1657 (Reactome)
Cyclin E2 Cdk2 complexREACT_384 (Reactome)
Cyclin E2 phospho-Cdk2 complexArrowREACT_384 (Reactome)
Cyclin EREACT_1683 (Reactome)
DDKREACT_2227 (Reactome)
DDKmim-catalysisREACT_907 (Reactome)
DNA Replication Factor AREACT_789 (Reactome)
DNA polymerase alpha primaseArrowREACT_1408 (Reactome)
DNA polymerase alpha primaseREACT_929 (Reactome)
DNA polymerase epsilon origin complexREACT_929 (Reactome)
DNA polymerase epsilonREACT_1344 (Reactome)
DP-1 E2F1/2/3ArrowREACT_1882 (Reactome)
DREAM complexTBarREACT_111167 (Reactome)
DYRK1Amim-catalysisREACT_111075 (Reactome)
E2F1 TFDP1ArrowREACT_22145 (Reactome)
E2F1 TFDP1REACT_1277 (Reactome)
E2F1ArrowREACT_111167 (Reactome)
E2F1ArrowREACT_111173 (Reactome)
E2F4 TFDP1,TFDP2ArrowREACT_111248 (Reactome)
E2F4/5 DP1/2ArrowREACT_111206 (Reactome)
H2OREACT_111148 (Reactome)
H2OREACT_111170 (Reactome)
H2OREACT_592 (Reactome)
HDAC1

RBL1 E2F4

TFDP1,TFDP2
TBarREACT_111173 (Reactome)
HDAC1

RBL2 E2F4/5

DP1/2
TBarREACT_111173 (Reactome)
HDAC1REACT_111037 (Reactome)
HDAC1REACT_111090 (Reactome)
INK4AREACT_7947 (Reactome)
MCM10REACT_541 (Reactome)
MYBL2ArrowREACT_111173 (Reactome)
Mcm10 active pre-replicative complexArrowREACT_951 (Reactome)
Mcm10 active pre-replicative complexREACT_2227 (Reactome)
Mcm2-7 complexREACT_907 (Reactome)
MuvB complexREACT_111075 (Reactome)
Myc/Max heterodimerArrowREACT_9013 (Reactome)
ORC originREACT_555 (Reactome)
PCNAArrowREACT_111167 (Reactome)
PKMYT1mim-catalysisREACT_1657 (Reactome)
PKMYT1mim-catalysisREACT_384 (Reactome)
PP2Amim-catalysisREACT_111148 (Reactome)
PP2Amim-catalysisREACT_111170 (Reactome)
PP2Amim-catalysisREACT_421 (Reactome)
PiArrowREACT_111148 (Reactome)
PiArrowREACT_111170 (Reactome)
PiArrowREACT_592 (Reactome)
RB1REACT_9050 (Reactome)
RBL1

E2F4

TFDP1,TFDP2
REACT_111039 (Reactome)
RBL1

E2F4

TFDP1,TFDP2
REACT_111090 (Reactome)
RBL1

E2F4

TFDP1,TFDP2
REACT_111248 (Reactome)
RBL1ArrowREACT_111148 (Reactome)
RBL1ArrowREACT_111167 (Reactome)
RBL1REACT_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)
RBL2ArrowREACT_111170 (Reactome)
RBL2REACT_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 damageArrowREACT_1408 (Reactome)
RNA primer-DNA primer origin duplex with DNA damageREACT_421 (Reactome)
RPA

Cdc45 CDK DDK Mcm10

pre-replicative complex
ArrowREACT_1344 (Reactome)
RPA

Cdc45 CDK DDK Mcm10

pre-replicative complex
ArrowREACT_929 (Reactome)
Rb-E2F1/2/3 DP-1 complexREACT_1882 (Reactome)
Rb1

RNA primer-DNA primer

origin duplex with DNA damage
REACT_1277 (Reactome)
SCFArrowREACT_111089 (Reactome)
SCFArrowREACT_9034 (Reactome)
SCFREACT_111194 (Reactome)
SCFREACT_9017 (Reactome)
SCFREACT_9060 (Reactome)
TOP2AArrowREACT_111167 (Reactome)
Ub-p-T401,S672,1035-RBL2ArrowREACT_111089 (Reactome)
WEE1mim-catalysisREACT_773 (Reactome)
origin of replicationREACT_1344 (Reactome)
p-MuvB complexArrowREACT_111075 (Reactome)
p-MuvB complexREACT_111236 (Reactome)
p-S795-RB1ArrowREACT_1882 (Reactome)
p-S795-RB1REACT_421 (Reactome)
p-T369,S640,S964,S975-RBL1ArrowREACT_111248 (Reactome)
p-T369,S640,S964,S975-RBL1REACT_111148 (Reactome)
p-T401,S672,1035-RBL2 SCFREACT_111089 (Reactome)
p-T401,S672,1035-RBL2 SCFmim-catalysisREACT_111089 (Reactome)
p-T401,S672,S1035-RBL2ArrowREACT_111206 (Reactome)
p-T401,S672,S1035-RBL2REACT_111170 (Reactome)
p-T401,S672,S1035-RBL2REACT_111194 (Reactome)
p21/p27REACT_2081 (Reactome)
p21/p27REACT_334 (Reactome)
p21/p27mim-catalysisREACT_334 (Reactome)
phosphorylated Mcm2-7 complexArrowREACT_907 (Reactome)
pre-replicative complexREACT_541 (Reactome)
ubiquitinArrowREACT_9034 (Reactome)
ubiquitinREACT_111089 (Reactome)
ubiquitinREACT_9026 (Reactome)
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