Regulation of mRNA stability by proteins that bind AU-rich elements (Homo sapiens)

From WikiPathways

Revision as of 19:50, 31 October 2018 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
36, 47, 49, 6218, 22, 3219, 52, 58, 6426, 38, 44425, 426, 43, 50, 5738, 40, 4412, 17, 29, 54, 633, 16, 26, 432018, 23, 24, 6013, 5418, 24, 41, 486, 8-10, 25...5631, 35, 37, 46, 616415, 21, 33, 40, 6519, 52562, 4, 7, 23, 30...19, 52, 58641331, 35, 37, 613, 16, 28, 43nucleoplasmcytosolPSMF1 p-T180,Y182-MAPK11 mRNA TranscriptTargeted by HuRPhosphorylated onSer158 and Ser318.UBC(305-380) mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 ZFP36L1 p-S158,S221-ELAVL1HSPB1 Phosphorylated KSRP(Ser193):14-3-3zetaComplexPSMB6 EXOSC3 p-S60,S186-ZFP36 ADPp-S92,S203-ZFP36L1 UBC(381-456) PSMD7 PSMA3 PRKCAPhosphorylated BRF1(Ser92,Ser203):mRNAComplexPSMB4 PSMA2 HSPA1A EXOSC5 EIF4G1 p-S83,S87-Ub-HNRNPD-3 p-S221,S318-ELAVL1 EXOSC6 YWHAZXPO1 p-T244-TNFSF13ELAVL1 EXOSC2 ELAVL1 HuR with UnknownPhosphorylation:mRNA ComplexUBB(77-152) mRNA Transcript Targeted by AUF1(hnRNP D0) DIS3 mRNA TranscriptTargeted byAUF1(hnRNP D0)ADPp-S193-KHSRP EXOSC1 p-S92,S203-ZFP36L1 p-S193-KHSRPmRNA Transcript Targeted by AUF1(hnRNP D0) KSRPEXOSC6 PSMB9 p-T180,Y182-MAPK14 Mg2+ ELAVL1 DCP1A UBB(153-228) PSMC4 mRNA Transcript Targeted by Tristetraproline EXOSC9 Phosphorylated BRF1(Ser54, Ser92,Ser203):mRNA:14-3-3ComplexPSMB3 PRKCD(1-676)PSMA8 PSMC3 DIS3 mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 YWHAB PABPC1PSMD8 mRNA Transcript Targeted by KSRP p-S60,S186-ZFP36 PSME4 PSMD5 YWHAZ ELAVL1EXOSC3 DCP1AHSPA8PSMD1 PSMD10 mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 UBC(457-532) PSMB11 UBC(609-684) SET PSME2 EXOSC1 YWHABTNPO1 p-S54,S92,S203-p-ZFP36L1 YWHAB p-S83,S87-HNRNPD-3 Exosome ComplexEXOSC1 Ubiquitinated AUF1Tetramer:Destabilized mRNAComplexp-S83,S87-HNRNPD-3 mRNA Transcript Targeted by BRF1 HSPA1AAUF1 Dimer (isoformp37 or p40)UBC(1-76) EXOSC8 mRNA TranscriptTargeted by BRF1TTP:mRNA DegradationComplexmRNA Transcript Targeted by HuR with Unknown Phosphorylation TNPO1EXOSC5 PSMB2 EXOSC5 PSMA4 HuR:mRNA ComplexPSME1 p-T244-TNFSF13mRNA Transcript Targeted by HuR with Unknown Phosphorylation mRNA Transcript Targeted by HuR with Unknown Phosphorylation EXOSC2 EXOSC8 PSMB1 EXOSC2 p-S272,T222,T334-MAPKAPK2mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318. mRNA Transcript Targeted by Tristetraproline PSMB8 RPS27A(1-76) HuRwithphosphoserine221andphosphoserine158:mRNA ComplexmRNA Transcript Targeted by BRF1 TTP:mRNA ComplexCD83 mRNA 001 p-S221,S318-ELAVL1 Phosphorylated BRF1(Ser54, Ser92,Ser203):mRNAComplexmRNA Transcript Targeted by KSRP AUF1 Tetramer:Destabilized mRNAComplex26S proteasomePARNPhospho-MAP kinasep38 (Mg2+ cofactor)EXOSC9 PSMC1 mRNA Transcript Targeted by BRF1 XPO1ADPp-S54,S92,S203-p-ZFP36L1 DCP2 KSRP PSMC5 EXOSC7 mRNA Transcript Targeted by Tristetraproline EXOSC5 TNPO1 ZFP36 p-S158,S221-ELAVL1 ENPP2 mRNA 001 TNPO1 mRNA Transcript Targeted by BRF1 KSRP p-S83,S87-HNRNPD-3 ATPEXOSC3 ZFP36L1p-T692-KHSRPHuR:APRIL:pp32:SET(SETalpha):Nup214(SETbeta):CRM1YWHAB PSMA6 p-S158,S221-ELAVL1 EXOSC4 PSMD11 EXOSC9 ZFP36 UBB(1-76) DCP2 GPRC5A mRNA 001 EXOSC8 AUF1 Complexed withTranslation andHeat Shock ProteinsEXOSC7 BRF1:mRNADegradation ComplexmRNA Transcript Targeted by BRF1 TNPO1 PSMA1 ANP32A EXOSC1 mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318. UBC(229-304) PABPC1 ZFP36L1 UBC(533-608) PSMD14 PSMB10 EXOSC7 p-S158,S221-ELAVL1 EXOSC4 mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318 mRNA TranscriptTargeted byTristetraprolineXRN1DIS3 p-S221,S318-ELAVL1 p-S221,S318-ELAVL1p-T308,S473-AKT1XRN1 UBC(153-228) PSMD4 NUP214 mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318. mRNA Transcript Targeted by AUF1(hnRNP D0) KSRP:mRNA ComplexUbHSPA8 Ub-HNRNPD-4 EXOSC4 PSME3 DCP2 mRNA TranscriptTargeted by HuRPhosphorylated onSer221 and Ser318PSMC6 EXOSC4 EXOSC6 PhosphorylatedTTP:mRNA ComplexHuR:mRNA complexesHuRwithphosphoserine221andphosphoserine318:mRNA ComplexANP32AHNRNPD-4 PhosphorylatedTTP:mRNA:14-3-3ComplexmRNA TranscriptTargeted by HuRwith UnknownPhosphorylationADPBRF1:mRNA ComplexATPKSRP:mRNADegradation ComplexDCP2SHFM1 HSPB1HNRNPD-4 PSMD3 EXOSC8 PSMA5 XRN1 p-S158,S221-ELAVL1 DCP1A PSMD2 PSMD12 DIS3 PSMA7 NUP214mRNA TranscriptTargeted by KSRPSETHNRNPD-4 PARN EXOSC7 ZFP36EXOSC6 UBC(77-152) ATPPSMD13 p-S221,S318-ELAVL1 EXOSC2 mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 EXOSC3 PSMB5 EXOSC9 ELAVL1 p-T244-TNFSF13 PSMC2 EIF4G1ATPmRNA Transcript Targeted by Tristetraproline PSMB7 UBA52(1-76) Phosphorylated BRF1(Ser92,Ser203):mRNA:14-3-3ComplexPSMD6 PSMD9 mRNA Transcript Targeted by BRF1 64325612, 17, 29, 545218, 2418, 641, 25, 26, 34, 55...5212, 17, 29, 5442, 56562, 4, 7, 39, 51...1, 25, 26, 34, 55...525, 426123, 485619, 52, 646, 43, 5018, 645, 423, 16, 28, 43, 5018, 641418, 2423, 485, 42, 5628, 50561, 25, 26, 34, 55...4013, 5412, 17, 29, 5418, 6418, 6419, 52248, 501856545, 425, 425623, 4818, 6423, 481, 25, 26, 34, 55...525, 4219, 5218, 645, 42, 565, 4211, 146123, 48


Description

RNA elements rich in adenine and uracil residues (AU-rich elements) bind specific proteins which either target the RNA for degradation or, more rarely, stabilize the RNA. The activity of the AU-element binding proteins is regulated, usually by phosphorylation but also by subcellular localization. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 450531
Reactome-version 
Reactome version: 65
Reactome Author 
Reactome Author: May, Bruce

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Laroia G, Schneider RJ.; ''Alternate exon insertion controls selective ubiquitination and degradation of different AUF1 protein isoforms.''; PubMed Europe PMC Scholia
  2. Sinsimer KS, Gratacós FM, Knapinska AM, Lu J, Krause CD, Wierzbowski AV, Maher LR, Scrudato S, Rivera YM, Gupta S, Turrin DK, De La Cruz MP, Pestka S, Brewer G.; ''Chaperone Hsp27, a novel subunit of AUF1 protein complexes, functions in AU-rich element-mediated mRNA decay.''; PubMed Europe PMC Scholia
  3. Emmons J, Townley-Tilson WH, Deleault KM, Skinner SJ, Gross RH, Whitfield ML, Brooks SA.; ''Identification of TTP mRNA targets in human dendritic cells reveals TTP as a critical regulator of dendritic cell maturation.''; PubMed Europe PMC Scholia
  4. Doller A, Akool el-S, Huwiler A, Müller R, Radeke HH, Pfeilschifter J, Eberhardt W.; ''Posttranslational modification of the AU-rich element binding protein HuR by protein kinase Cdelta elicits angiotensin II-induced stabilization and nuclear export of cyclooxygenase 2 mRNA.''; PubMed Europe PMC Scholia
  5. López de Silanes I, Zhan M, Lal A, Yang X, Gorospe M.; ''Identification of a target RNA motif for RNA-binding protein HuR.''; PubMed Europe PMC Scholia
  6. Wilson GM, Lu J, Sutphen K, Suarez Y, Sinha S, Brewer B, Villanueva-Feliciano EC, Ysla RM, Charles S, Brewer G.; ''Phosphorylation of p40AUF1 regulates binding to A + U-rich mRNA-destabilizing elements and protein-induced changes in ribonucleoprotein structure.''; PubMed Europe PMC Scholia
  7. Chang WL, Tarn WY.; ''A role for transportin in deposition of TTP to cytoplasmic RNA granules and mRNA decay.''; PubMed Europe PMC Scholia
  8. Laroia G, Sarkar B, Schneider RJ.; ''Ubiquitin-dependent mechanism regulates rapid turnover of AU-rich cytokine mRNAs.''; PubMed Europe PMC Scholia
  9. Fries B, Heukeshoven J, Hauber I, Grüttner C, Stocking C, Kehlenbach RH, Hauber J, Chemnitz J.; ''Analysis of nucleocytoplasmic trafficking of the HuR ligand APRIL and its influence on CD83 expression.''; PubMed Europe PMC Scholia
  10. 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
  11. Stoecklin G, Colombi M, Raineri I, Leuenberger S, Mallaun M, Schmidlin M, Gross B, Lu M, Kitamura T, Moroni C.; ''Functional cloning of BRF1, a regulator of ARE-dependent mRNA turnover.''; PubMed Europe PMC Scholia
  12. Sarkar B, Xi Q, He C, Schneider RJ.; ''Selective degradation of AU-rich mRNAs promoted by the p37 AUF1 protein isoform.''; PubMed Europe PMC Scholia
  13. Michel SL, Guerrerio AL, Berg JM.; ''Selective RNA binding by a single CCCH zinc-binding domain from Nup475 (Tristetraprolin).''; PubMed Europe PMC Scholia
  14. Chrestensen CA, Schroeder MJ, Shabanowitz J, Hunt DF, Pelo JW, Worthington MT, Sturgill TW.; ''MAPKAP kinase 2 phosphorylates tristetraprolin on in vivo sites including Ser178, a site required for 14-3-3 binding.''; PubMed Europe PMC Scholia
  15. Pautz A, Linker K, Altenhöfer S, Heil S, Schmidt N, Art J, Knauer S, Stauber R, Sadri N, Pont A, Schneider RJ, Kleinert H.; ''Similar regulation of human inducible nitric-oxide synthase expression by different isoforms of the RNA-binding protein AUF1.''; PubMed Europe PMC Scholia
  16. Cao H, Deterding LJ, Venable JD, Kennington EA, Yates JR, Tomer KB, Blackshear PJ.; ''Identification of the anti-inflammatory protein tristetraprolin as a hyperphosphorylated protein by mass spectrometry and site-directed mutagenesis.''; PubMed Europe PMC Scholia
  17. García-Mayoral MF, Díaz-Moreno I, Hollingworth D, Ramos A.; ''The sequence selectivity of KSRP explains its flexibility in the recognition of the RNA targets.''; PubMed Europe PMC Scholia
  18. Lai WS, Kennington EA, Blackshear PJ.; ''Tristetraprolin and its family members can promote the cell-free deadenylation of AU-rich element-containing mRNAs by poly(A) ribonuclease.''; PubMed Europe PMC Scholia
  19. Prechtel AT, Chemnitz J, Schirmer S, Ehlers C, Langbein-Detsch I, Stülke J, Dabauvalle MC, Kehlenbach RH, Hauber J.; ''Expression of CD83 is regulated by HuR via a novel cis-active coding region RNA element.''; PubMed Europe PMC Scholia
  20. Brewer BY, Malicka J, Blackshear PJ, Wilson GM.; ''RNA sequence elements required for high affinity binding by the zinc finger domain of tristetraprolin: conformational changes coupled to the bipartite nature of Au-rich MRNA-destabilizing motifs.''; PubMed Europe PMC Scholia
  21. Wilson GM, Sutphen K, Chuang Ky, Brewer G.; ''Folding of A+U-rich RNA elements modulates AUF1 binding. Potential roles in regulation of mRNA turnover.''; PubMed Europe PMC Scholia
  22. Stoecklin G, Stubbs T, Kedersha N, Wax S, Rigby WF, Blackwell TK, Anderson P.; ''MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay.''; PubMed Europe PMC Scholia
  23. Benjamin D, Schmidlin M, Min L, Gross B, Moroni C.; ''BRF1 protein turnover and mRNA decay activity are regulated by protein kinase B at the same phosphorylation sites.''; PubMed Europe PMC Scholia
  24. Worthington MT, Pelo JW, Sachedina MA, Applegate JL, Arseneau KO, Pizarro TT.; ''RNA binding properties of the AU-rich element-binding recombinant Nup475/TIS11/tristetraprolin protein.''; PubMed Europe PMC Scholia
  25. Li H, Chen W, Zhou Y, Abidi P, Sharpe O, Robinson WH, Kraemer FB, Liu J.; ''Identification of mRNA binding proteins that regulate the stability of LDL receptor mRNA through AU-rich elements.''; PubMed Europe PMC Scholia
  26. Díaz-Moreno I, Hollingworth D, Frenkiel TA, Kelly G, Martin S, Howell S, García-Mayoral M, Gherzi R, Briata P, Ramos A.; ''Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding.''; PubMed Europe PMC Scholia
  27. Wilson GM, Lu J, Sutphen K, Sun Y, Huynh Y, Brewer G.; ''Regulation of A + U-rich element-directed mRNA turnover involving reversible phosphorylation of AUF1.''; PubMed Europe PMC Scholia
  28. Gherzi R, Lee KY, Briata P, Wegmüller D, Moroni C, Karin M, Chen CY.; ''A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery.''; PubMed Europe PMC Scholia
  29. Zhang W, Wagner BJ, Ehrenman K, Schaefer AW, DeMaria CT, Crater D, DeHaven K, Long L, Brewer G.; ''Purification, characterization, and cDNA cloning of an AU-rich element RNA-binding protein, AUF1.''; PubMed Europe PMC Scholia
  30. Gherzi R, Trabucchi M, Ponassi M, Ruggiero T, Corte G, Moroni C, Chen CY, Khabar KS, Andersen JS, Briata P.; ''The RNA-binding protein KSRP promotes decay of beta-catenin mRNA and is inactivated by PI3K-AKT signaling.''; PubMed Europe PMC Scholia
  31. Lai WS, Carballo E, Strum JR, Kennington EA, Phillips RS, Blackshear PJ.; ''Evidence that tristetraprolin binds to AU-rich elements and promotes the deadenylation and destabilization of tumor necrosis factor alpha mRNA.''; PubMed Europe PMC Scholia
  32. Cao H, Dzineku F, Blackshear PJ.; ''Expression and purification of recombinant tristetraprolin that can bind to tumor necrosis factor-alpha mRNA and serve as a substrate for mitogen-activated protein kinases.''; PubMed Europe PMC Scholia
  33. Chemnitz J, Pieper D, Grüttner C, Hauber J.; ''Phosphorylation of the HuR ligand APRIL by casein kinase 2 regulates CD83 expression.''; PubMed Europe PMC Scholia
  34. Doller A, Schlepckow K, Schwalbe H, Pfeilschifter J, Eberhardt W.; ''Tandem phosphorylation of serines 221 and 318 by protein kinase Cdelta coordinates mRNA binding and nucleocytoplasmic shuttling of HuR.''; PubMed Europe PMC Scholia
  35. Lal A, Mazan-Mamczarz K, Kawai T, Yang X, Martindale JL, Gorospe M.; ''Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs.''; PubMed Europe PMC Scholia
  36. Lykke-Andersen J, Wagner E.; ''Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1.''; PubMed Europe PMC Scholia
  37. Barreau C, Paillard L, Osborne HB.; ''AU-rich elements and associated factors: are there unifying principles?''; PubMed Europe PMC Scholia
  38. Lapucci A, Donnini M, Papucci L, Witort E, Tempestini A, Bevilacqua A, Nicolin A, Brewer G, Schiavone N, Capaccioli S.; ''AUF1 Is a bcl-2 A + U-rich element-binding protein involved in bcl-2 mRNA destabilization during apoptosis.''; PubMed Europe PMC Scholia
  39. Lu JY, Bergman N, Sadri N, Schneider RJ.; ''Assembly of AUF1 with eIF4G-poly(A) binding protein complex suggests a translation function in AU-rich mRNA decay.''; PubMed Europe PMC Scholia
  40. DeMaria CT, Sun Y, Long L, Wagner BJ, Brewer G.; ''Structural determinants in AUF1 required for high affinity binding to A + U-rich elements.''; PubMed Europe PMC Scholia
  41. Schmidlin M, Lu M, Leuenberger SA, Stoecklin G, Mallaun M, Gross B, Gherzi R, Hess D, Hemmings BA, Moroni C.; ''The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B.''; PubMed Europe PMC Scholia
  42. Franks TM, Lykke-Andersen J.; ''TTP and BRF proteins nucleate processing body formation to silence mRNAs with AU-rich elements.''; PubMed Europe PMC Scholia
  43. Goldberg-Cohen I, Furneauxb H, Levy AP.; ''A 40-bp RNA element that mediates stabilization of vascular endothelial growth factor mRNA by HuR.''; PubMed Europe PMC Scholia
  44. Brennan CM, Gallouzi IE, Steitz JA.; ''Protein ligands to HuR modulate its interaction with target mRNAs in vivo.''; PubMed Europe PMC Scholia
  45. Bevilacqua A, Ceriani MC, Capaccioli S, Nicolin A.; ''Post-transcriptional regulation of gene expression by degradation of messenger RNAs.''; PubMed Europe PMC Scholia
  46. Blackshear PJ, Lai WS, Kennington EA, Brewer G, Wilson GM, Guan X, Zhou P.; ''Characteristics of the interaction of a synthetic human tristetraprolin tandem zinc finger peptide with AU-rich element-containing RNA substrates.''; PubMed Europe PMC Scholia
  47. Laroia G, Cuesta R, Brewer G, Schneider RJ.; ''Control of mRNA decay by heat shock-ubiquitin-proteasome pathway.''; PubMed Europe PMC Scholia
  48. Doller A, Huwiler A, Müller R, Radeke HH, Pfeilschifter J, Eberhardt W.; ''Protein kinase C alpha-dependent phosphorylation of the mRNA-stabilizing factor HuR: implications for posttranscriptional regulation of cyclooxygenase-2.''; PubMed Europe PMC Scholia
  49. Liao B, Hu Y, Brewer G.; ''Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation.''; PubMed Europe PMC Scholia
  50. Schmidt N, Pautz A, Art J, Rauschkolb P, Jung M, Erkel G, Goldring MB, Kleinert H.; ''Transcriptional and post-transcriptional regulation of iNOS expression in human chondrocytes.''; PubMed Europe PMC Scholia
  51. Suswam EA, Nabors LB, Huang Y, Yang X, King PH.; ''IL-1beta induces stabilization of IL-8 mRNA in malignant breast cancer cells via the 3' untranslated region: Involvement of divergent RNA-binding factors HuR, KSRP and TIAR.''; PubMed Europe PMC Scholia
  52. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  53. Gingerich TJ, Feige JJ, LaMarre J.; ''AU-rich elements and the control of gene expression through regulated mRNA stability.''; PubMed Europe PMC Scholia
  54. Fialcowitz-White EJ, Brewer BY, Ballin JD, Willis CD, Toth EA, Wilson GM.; ''Specific protein domains mediate cooperative assembly of HuR oligomers on AU-rich mRNA-destabilizing sequences.''; PubMed Europe PMC Scholia
  55. Raineri I, Wegmueller D, Gross B, Certa U, Moroni C.; ''Roles of AUF1 isoforms, HuR and BRF1 in ARE-dependent mRNA turnover studied by RNA interference.''; PubMed Europe PMC Scholia
  56. Sandler H, Stoecklin G.; ''Control of mRNA decay by phosphorylation of tristetraprolin.''; PubMed Europe PMC Scholia
  57. Rigby WF, Roy K, Collins J, Rigby S, Connolly JE, Bloch DB, Brooks SA.; ''Structure/function analysis of tristetraprolin (TTP): p38 stress-activated protein kinase and lipopolysaccharide stimulation do not alter TTP function.''; PubMed Europe PMC Scholia
  58. Briata P, Forcales SV, Ponassi M, Corte G, Chen CY, Karin M, Puri PL, Gherzi R.; ''p38-dependent phosphorylation of the mRNA decay-promoting factor KSRP controls the stability of select myogenic transcripts.''; PubMed Europe PMC Scholia
  59. Maitra S, Chou CF, Luber CA, Lee KY, Mann M, Chen CY.; ''The AU-rich element mRNA decay-promoting activity of BRF1 is regulated by mitogen-activated protein kinase-activated protein kinase 2.''; PubMed Europe PMC Scholia
  60. Wilson GM, Sun Y, Lu H, Brewer G.; ''Assembly of AUF1 oligomers on U-rich RNA targets by sequential dimer association.''; PubMed Europe PMC Scholia
  61. Zhang T, Kruys V, Huez G, Gueydan C.; ''AU-rich element-mediated translational control: complexity and multiple activities of trans-activating factors.''; PubMed Europe PMC Scholia
  62. Chen CY, Gherzi R, Ong SE, Chan EL, Raijmakers R, Pruijn GJ, Stoecklin G, Moroni C, Mann M, Karin M.; ''AU binding proteins recruit the exosome to degrade ARE-containing mRNAs.''; PubMed Europe PMC Scholia
  63. Skriner K, Hueber W, Süleymanoglu E, Höfler E, Krenn V, Smolen J, Steiner G.; ''AUF1, the regulator of tumor necrosis factor alpha messenger RNA decay, is targeted by autoantibodies of patients with systemic rheumatic diseases.''; PubMed Europe PMC Scholia
  64. Hau HH, Walsh RJ, Ogilvie RL, Williams DA, Reilly CS, Bohjanen PR.; ''Tristetraprolin recruits functional mRNA decay complexes to ARE sequences.''; PubMed Europe PMC Scholia
  65. Chou CF, Mulky A, Maitra S, Lin WJ, Gherzi R, Kappes J, Chen CY.; ''Tethering KSRP, a decay-promoting AU-rich element-binding protein, to mRNAs elicits mRNA decay.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114931view16:45, 25 January 2021ReactomeTeamReactome version 75
113376view11:45, 2 November 2020ReactomeTeamReactome version 74
112581view15:55, 9 October 2020ReactomeTeamReactome version 73
101496view11:36, 1 November 2018ReactomeTeamreactome version 66
101033view21:17, 31 October 2018ReactomeTeamreactome version 65
100566view19:50, 31 October 2018ReactomeTeamreactome version 64
100115view16:36, 31 October 2018ReactomeTeamreactome version 63
99665view15:06, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99263view12:45, 31 October 2018ReactomeTeamreactome version 62
93782view13:36, 16 August 2017ReactomeTeamreactome version 61
93315view11:20, 9 August 2017ReactomeTeamreactome version 61
88143view12:58, 26 July 2016RyanmillerOntology Term : 'regulatory pathway' added !
86400view09:17, 11 July 2016ReactomeTeamreactome version 56
83344view10:52, 18 November 2015ReactomeTeamVersion54
81764view10:10, 26 August 2015ReactomeTeamVersion53
76960view08:24, 17 July 2014ReactomeTeamFixed remaining interactions
76665view12:03, 16 July 2014ReactomeTeamFixed remaining interactions
75994view10:05, 11 June 2014ReactomeTeamRe-fixing comment source
75697view11:03, 10 June 2014ReactomeTeamReactome 48 Update
75053view13:56, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74833view10:05, 30 April 2014ReactomeTeamReactome46
74697view08:46, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-68819 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ANP32A ProteinP39687 (Uniprot-TrEMBL)
ANP32AProteinP39687 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
AUF1 Complexed with

Translation and

Heat Shock Proteins		ComplexR-HSA-450623 (Reactome)
AUF1 Dimer (isoform p37 or p40)ComplexR-HSA-450391 (Reactome) Phosphorylated isoform p40 of AUF1 destabilizes mRNA. Isoform p37 (phosphorylation unknown) also destabilizes mRNA.
AUF1 Tetramer:

Destabilized mRNA

Complex		ComplexR-HSA-450598 (Reactome)
BRF1:mRNA Degradation ComplexComplexR-HSA-450430 (Reactome)
BRF1:mRNA ComplexComplexR-HSA-450589 (Reactome)
CD83 mRNA 001 R-HSA-450486 (Reactome)
DCP1A ProteinQ9NPI6 (Uniprot-TrEMBL)
DCP1AProteinQ9NPI6 (Uniprot-TrEMBL)
DCP2 ProteinQ8IU60 (Uniprot-TrEMBL)
DCP2ProteinQ8IU60 (Uniprot-TrEMBL)
DIS3 ProteinQ9Y2L1 (Uniprot-TrEMBL)
EIF4G1 ProteinQ04637 (Uniprot-TrEMBL)
EIF4G1ProteinQ04637 (Uniprot-TrEMBL)
ELAVL1 ProteinQ15717 (Uniprot-TrEMBL)
ELAVL1ProteinQ15717 (Uniprot-TrEMBL)
ENPP2 mRNA 001 ProteinENST00000427067 (Ensembl)
EXOSC1 ProteinQ9Y3B2 (Uniprot-TrEMBL)
EXOSC2 ProteinQ13868 (Uniprot-TrEMBL)
EXOSC3 ProteinQ9NQT5 (Uniprot-TrEMBL)
EXOSC4 ProteinQ9NPD3 (Uniprot-TrEMBL)
EXOSC5 ProteinQ9NQT4 (Uniprot-TrEMBL)
EXOSC6 ProteinQ5RKV6 (Uniprot-TrEMBL)
EXOSC7 ProteinQ15024 (Uniprot-TrEMBL)
EXOSC8 ProteinQ96B26 (Uniprot-TrEMBL)
EXOSC9 ProteinQ06265 (Uniprot-TrEMBL)
Exosome ComplexComplexR-HSA-429971 (Reactome) The exosome complex comprises a ring and associated subunits. The ring contains EXOSC2, EXOSC7, EXOSC8, EXOSC9, EXOSC5, and EXOSC6. The subunits EXOSC1, EXOSC2, EXOSC3, and RRP44 bind the ring. The catalytic ribonuclease site is located in RRP44, which yields ribonucleotides having 5'-monophosphates.
GPRC5A mRNA 001 ProteinENST00000014914 (Ensembl)
HNRNPD-4 ProteinQ14103-4 (Uniprot-TrEMBL)
HSPA1A ProteinP0DMV8 (Uniprot-TrEMBL)
HSPA1AProteinP0DMV8 (Uniprot-TrEMBL)
HSPA8 ProteinP11142 (Uniprot-TrEMBL)
HSPA8ProteinP11142 (Uniprot-TrEMBL)
HSPB1 ProteinP04792 (Uniprot-TrEMBL)
HSPB1ProteinP04792 (Uniprot-TrEMBL)
HuR

with phosphoserine221 and

phosphoserine158:mRNA Complex		ComplexR-HSA-517672 (Reactome)
HuR

with phosphoserine221 and

phosphoserine318:mRNA Complex		ComplexR-HSA-517751 (Reactome)
HuR with Unknown

Phosphorylation:

mRNA Complex		ComplexR-HSA-450395 (Reactome)
HuR:APRIL:pp32:SET(SETalpha):Nup214(SETbeta):CRM1ComplexR-HSA-450537 (Reactome)
HuR:mRNA ComplexComplexR-HSA-517713 (Reactome)
HuR:mRNA complexesComplexR-HSA-517615 (Reactome)
KSRP ProteinQ92945 (Uniprot-TrEMBL)
KSRP:mRNA Degradation ComplexComplexR-HSA-450479 (Reactome)
KSRP:mRNA ComplexComplexR-HSA-450608 (Reactome)
KSRPProteinQ92945 (Uniprot-TrEMBL)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
NUP214 ProteinP35658 (Uniprot-TrEMBL)
NUP214ProteinP35658 (Uniprot-TrEMBL)
PABPC1 ProteinP11940 (Uniprot-TrEMBL)
PABPC1ProteinP11940 (Uniprot-TrEMBL)
PARN ProteinO95453 (Uniprot-TrEMBL)
PARNProteinO95453 (Uniprot-TrEMBL)
PRKCAProteinP17252 (Uniprot-TrEMBL)
PRKCD(1-676)ProteinQ05655 (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)
PSMA8 ProteinQ8TAA3 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB11 ProteinA5LHX3 (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)
PSME4 ProteinQ14997 (Uniprot-TrEMBL)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
Phospho-MAP kinase p38 (Mg2+ cofactor)ComplexR-HSA-170993 (Reactome)
Phosphorylated TTP:mRNA ComplexComplexR-HSA-450541 (Reactome)
Phosphorylated

TTP:mRNA:14-3-3

Complex		ComplexR-HSA-450420 (Reactome)
Phosphorylated BRF1

(Ser54, Ser92, Ser203):mRNA

Complex		ComplexR-HSA-450502 (Reactome)
Phosphorylated BRF1

(Ser54, Ser92, Ser203):mRNA:14-3-3

Complex		ComplexR-HSA-482787 (Reactome)
Phosphorylated BRF1

(Ser92, Ser203):mRNA

Complex		ComplexR-HSA-450378 (Reactome)
Phosphorylated BRF1

(Ser92, Ser203):mRNA:14-3-3

Complex		ComplexR-HSA-450585 (Reactome)
Phosphorylated KSRP

(Ser193):14-3-3zeta

Complex		ComplexR-HSA-450446 (Reactome)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
SET ProteinQ01105 (Uniprot-TrEMBL)
SETProteinQ01105 (Uniprot-TrEMBL)
SHFM1 ProteinP60896 (Uniprot-TrEMBL)
TNPO1 ProteinQ92973 (Uniprot-TrEMBL)
TNPO1ProteinQ92973 (Uniprot-TrEMBL)
TTP:mRNA ComplexComplexR-HSA-450365 (Reactome)
TTP:mRNA Degradation ComplexComplexR-HSA-450436 (Reactome)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-HNRNPD-4 ProteinQ14103-4 (Uniprot-TrEMBL)
UbComplexR-HSA-113595 (Reactome)
Ubiquitinated AUF1

Tetramer: Destabilized mRNA

Complex		ComplexR-HSA-450458 (Reactome)
XPO1 ProteinO14980 (Uniprot-TrEMBL)
XPO1ProteinO14980 (Uniprot-TrEMBL)
XRN1 ProteinQ8IZH2 (Uniprot-TrEMBL)
XRN1ProteinQ8IZH2 (Uniprot-TrEMBL)
YWHAB ProteinP31946 (Uniprot-TrEMBL)
YWHABProteinP31946 (Uniprot-TrEMBL)
YWHAZ ProteinP63104 (Uniprot-TrEMBL)
YWHAZProteinP63104 (Uniprot-TrEMBL)
ZFP36 ProteinP26651 (Uniprot-TrEMBL)
ZFP36L1 ProteinQ07352 (Uniprot-TrEMBL)
ZFP36L1ProteinQ07352 (Uniprot-TrEMBL)
ZFP36ProteinP26651 (Uniprot-TrEMBL)
mRNA Transcript

Targeted by

AUF1(hnRNP D0)		R-ALL-450444 (Reactome) AUF1 (hnRNP D0) binds AU-rich elements in mRNAs encoding Interleukin-1 beta (IL1B), Tumor Necrosis Factor alpha (TNFA), Cyclin-dependent kinase inhibitor 1 (CDNK1A, p21), Cyclin-D1 (CCND1), Granulocyte-macrophage colony stimulating factor (GM-CSF, CSF2), inducible Nitric oxide synthase (iNOS, NOS2), Proto-oncogene cFos (FOS), Myc proto-oncogene (MYC), Apoptosis regulator Bcl-2 (BCL2).
mRNA Transcript

Targeted by

Tristetraproline		R-ALL-450597 (Reactome) Tristetraproline binds AU-rich elements in the following mRNAs: Tumor necrosis factor alpha (TNFA), Granulocyte-macrophage colony stimulating factor (CSF2, GM-CSF), Interleukin-2 (IL-2), and Proto-oncogene C-FOS (FOS, c-fos).
mRNA Transcript Targeted by BRF1R-ALL-450523 (Reactome) BRF1 binds AU-rich elements in the following mRNAs: IL-3, CSF2 (GM-CSF).
mRNA Transcript

Targeted by HuR Phosphorylated on

Ser158 and Ser318.		R-ALL-450605 (Reactome) Phosphorylated HuR (phosphoserine158 and phosphoserine318) binds AU-rich elements in the Cyclooxygenase-2 (COX-2, PTGS2) mRNA.
mRNA Transcript

Targeted by HuR Phosphorylated on

Ser221 and Ser318		R-ALL-517622 (Reactome) Phosphorylated HuR (phosphoserine221 and phosphoserine318) binds AU-rich elements in the following mRNAs: Cyclooxygenase-2 (COX-2, PTGS2), Cyclin A (CCNA, CCNA2), and Cyclin D1 (CCND1).
mRNA Transcript

Targeted by HuR with Unknown

Phosphorylation		R-ALL-450613 (Reactome) HuR (phosphorylation state unknown) binds AU-rich elements in the following mRNAs: Antigen CD83 (CD83), Cyclin B1 (CCNB1), and proto-oncogene c-Fos (FOS).
mRNA Transcript Targeted by KSRPR-ALL-450386 (Reactome) KSRP binds AU-rich elements in the following mRNAs: IL-8, LDLR, and NOS2 (iNOS). Binding of KSRP to the mRNA encoding Beta-catenin is inferred from mouse.
mRNA Transcript Targeted by AUF1(hnRNP D0) R-ALL-450444 (Reactome) AUF1 (hnRNP D0) binds AU-rich elements in mRNAs encoding Interleukin-1 beta (IL1B), Tumor Necrosis Factor alpha (TNFA), Cyclin-dependent kinase inhibitor 1 (CDNK1A, p21), Cyclin-D1 (CCND1), Granulocyte-macrophage colony stimulating factor (GM-CSF, CSF2), inducible Nitric oxide synthase (iNOS, NOS2), Proto-oncogene cFos (FOS), Myc proto-oncogene (MYC), Apoptosis regulator Bcl-2 (BCL2).
mRNA Transcript Targeted by BRF1 R-ALL-450523 (Reactome) BRF1 binds AU-rich elements in the following mRNAs: IL-3, CSF2 (GM-CSF).
mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318 R-ALL-450425 (Reactome) Phosphorylated HuR (phosphoserine158 and phosphoserine318) binds AU-rich elements in the Cyclooxygenase-2 (COX-2, PTGS2) mRNA.
mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318. R-ALL-450605 (Reactome) Phosphorylated HuR (phosphoserine158 and phosphoserine318) binds AU-rich elements in the Cyclooxygenase-2 (COX-2, PTGS2) mRNA.
mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 R-ALL-517560 (Reactome) Phosphorylated HuR (phosphoserine221 and phosphoserine318) binds AU-rich elements in the following mRNAs: Cyclooxygenase-2 (COX-2, PTGS2), Cyclin A (CCNA, CCNA2), and Cyclin D1 (CCND1).
mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 R-ALL-517622 (Reactome) Phosphorylated HuR (phosphoserine221 and phosphoserine318) binds AU-rich elements in the following mRNAs: Cyclooxygenase-2 (COX-2, PTGS2), Cyclin A (CCNA, CCNA2), and Cyclin D1 (CCND1).
mRNA Transcript Targeted by HuR with Unknown Phosphorylation R-ALL-450613 (Reactome) HuR (phosphorylation state unknown) binds AU-rich elements in the following mRNAs: Antigen CD83 (CD83), Cyclin B1 (CCNB1), and proto-oncogene c-Fos (FOS).
mRNA Transcript Targeted by KSRP R-ALL-450386 (Reactome) KSRP binds AU-rich elements in the following mRNAs: IL-8, LDLR, and NOS2 (iNOS). Binding of KSRP to the mRNA encoding Beta-catenin is inferred from mouse.
mRNA Transcript Targeted by Tristetraproline R-ALL-450597 (Reactome) Tristetraproline binds AU-rich elements in the following mRNAs: Tumor necrosis factor alpha (TNFA), Granulocyte-macrophage colony stimulating factor (CSF2, GM-CSF), Interleukin-2 (IL-2), and Proto-oncogene C-FOS (FOS, c-fos).
p-S158,S221-ELAVL1 ProteinQ15717 (Uniprot-TrEMBL)
p-S158,S221-ELAVL1ProteinQ15717 (Uniprot-TrEMBL)
p-S193-KHSRP ProteinQ92945 (Uniprot-TrEMBL)
p-S193-KHSRPProteinQ92945 (Uniprot-TrEMBL)
p-S221,S318-ELAVL1 ProteinQ15717 (Uniprot-TrEMBL)
p-S221,S318-ELAVL1ProteinQ15717 (Uniprot-TrEMBL)
p-S272,T222,T334-MAPKAPK2ProteinP49137 (Uniprot-TrEMBL)
p-S54,S92,S203-p-ZFP36L1 ProteinQ07352 (Uniprot-TrEMBL)
p-S60,S186-ZFP36 ProteinP26651 (Uniprot-TrEMBL)
p-S83,S87-HNRNPD-3 ProteinQ14103-3 (Uniprot-TrEMBL)
p-S83,S87-Ub-HNRNPD-3 ProteinQ14103-3 (Uniprot-TrEMBL)
p-S92,S203-ZFP36L1 ProteinQ07352 (Uniprot-TrEMBL)
p-T180,Y182-MAPK11 ProteinQ15759 (Uniprot-TrEMBL)
p-T180,Y182-MAPK14 ProteinQ16539 (Uniprot-TrEMBL)
p-T244-TNFSF13 ProteinO75888 (Uniprot-TrEMBL)
p-T244-TNFSF13ProteinO75888 (Uniprot-TrEMBL)
p-T308,S473-AKT1ProteinP31749 (Uniprot-TrEMBL)
p-T692-KHSRPProteinQ92945 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisR-HSA-450466 (Reactome)
ADPArrowR-HSA-450463 (Reactome)
ADPArrowR-HSA-450474 (Reactome)
ADPArrowR-HSA-450490 (Reactome)
ADPArrowR-HSA-450499 (Reactome)
ADPArrowR-HSA-450533 (Reactome)
ADPArrowR-HSA-450550 (Reactome)
ADPArrowR-HSA-451152 (Reactome)
ANP32AR-HSA-450387 (Reactome)
ATPR-HSA-450463 (Reactome)
ATPR-HSA-450474 (Reactome)
ATPR-HSA-450490 (Reactome)
ATPR-HSA-450499 (Reactome)
ATPR-HSA-450533 (Reactome)
ATPR-HSA-450550 (Reactome)
ATPR-HSA-451152 (Reactome)
AUF1 Complexed with

Translation and

Heat Shock Proteins		ArrowR-HSA-450551 (Reactome)
AUF1 Complexed with

Translation and

Heat Shock Proteins		R-HSA-450580 (Reactome)
AUF1 Dimer (isoform p37 or p40)R-HSA-450434 (Reactome)
AUF1 Tetramer:

Destabilized mRNA

Complex		ArrowR-HSA-450434 (Reactome)
AUF1 Tetramer:

Destabilized mRNA

Complex		R-HSA-450551 (Reactome)
BRF1:mRNA Degradation ComplexArrowR-HSA-450488 (Reactome)
BRF1:mRNA ComplexArrowR-HSA-450517 (Reactome)
BRF1:mRNA ComplexR-HSA-450474 (Reactome)
BRF1:mRNA ComplexR-HSA-450488 (Reactome)
BRF1:mRNA ComplexR-HSA-450490 (Reactome)
DCP1AR-HSA-450431 (Reactome)
DCP1AR-HSA-450488 (Reactome)
DCP2R-HSA-450422 (Reactome)
DCP2R-HSA-450431 (Reactome)
DCP2R-HSA-450488 (Reactome)
EIF4G1R-HSA-450551 (Reactome)
ELAVL1R-HSA-450494 (Reactome)
ELAVL1R-HSA-450533 (Reactome)
ELAVL1R-HSA-450550 (Reactome)
Exosome ComplexR-HSA-450422 (Reactome)
Exosome ComplexR-HSA-450431 (Reactome)
Exosome ComplexR-HSA-450488 (Reactome)
HSPA1AR-HSA-450551 (Reactome)
HSPA8R-HSA-450551 (Reactome)
HSPB1R-HSA-450551 (Reactome)
HuR

with phosphoserine221 and

phosphoserine158:mRNA Complex		ArrowR-HSA-517674 (Reactome)
HuR

with phosphoserine221 and

phosphoserine318:mRNA Complex		ArrowR-HSA-517705 (Reactome)
HuR with Unknown

Phosphorylation:

mRNA Complex		ArrowR-HSA-450494 (Reactome)
HuR:APRIL:pp32:SET(SETalpha):Nup214(SETbeta):CRM1ArrowR-HSA-450387 (Reactome)
HuR:APRIL:pp32:SET(SETalpha):Nup214(SETbeta):CRM1R-HSA-450595 (Reactome)
HuR:mRNA ComplexArrowR-HSA-450595 (Reactome)
HuR:mRNA complexesR-HSA-450387 (Reactome)
KSRP:mRNA Degradation ComplexArrowR-HSA-450422 (Reactome)
KSRP:mRNA ComplexArrowR-HSA-450592 (Reactome)
KSRP:mRNA ComplexR-HSA-450422 (Reactome)
KSRPR-HSA-450499 (Reactome)
KSRPR-HSA-450592 (Reactome)
KSRPR-HSA-451152 (Reactome)
NUP214R-HSA-450387 (Reactome)
PABPC1R-HSA-450551 (Reactome)
PARNR-HSA-450422 (Reactome)
PRKCAmim-catalysisR-HSA-450550 (Reactome)
PRKCD(1-676)mim-catalysisR-HSA-450533 (Reactome)
Phospho-MAP kinase p38 (Mg2+ cofactor)mim-catalysisR-HSA-451152 (Reactome)
Phosphorylated TTP:mRNA ComplexArrowR-HSA-450463 (Reactome)
Phosphorylated TTP:mRNA ComplexR-HSA-450394 (Reactome)
Phosphorylated

TTP:mRNA:14-3-3

Complex		ArrowR-HSA-450394 (Reactome)
Phosphorylated BRF1

(Ser54, Ser92, Ser203):mRNA

Complex		ArrowR-HSA-450474 (Reactome)
Phosphorylated BRF1

(Ser54, Ser92, Ser203):mRNA

Complex		R-HSA-482788 (Reactome)
Phosphorylated BRF1

(Ser54, Ser92, Ser203):mRNA:14-3-3

Complex		ArrowR-HSA-482788 (Reactome)
Phosphorylated BRF1

(Ser92, Ser203):mRNA

Complex		ArrowR-HSA-450490 (Reactome)
Phosphorylated BRF1

(Ser92, Ser203):mRNA

Complex		R-HSA-450406 (Reactome)
Phosphorylated BRF1

(Ser92, Ser203):mRNA:14-3-3

Complex		ArrowR-HSA-450406 (Reactome)
Phosphorylated KSRP

(Ser193):14-3-3zeta

Complex		ArrowR-HSA-450620 (Reactome)
R-HSA-450387 (Reactome) HuR interacts with SETalpha (Template activating factor 1), SETbeta (CAN/Nup214), APRIL, pp32, and the nuclear export factor CRM1.
R-HSA-450394 (Reactome) Phosphorylated tristetraproline (TTP) binds 14-3-3, which inhibits the ability of TTP to destabilize RNA. Thus RNAs bound by TTP become stabilized. The binding of 14-3-3 causes TTP to be excluded from stress granules.
R-HSA-450400 (Reactome) Tristetraprolin (TTP) binds UUAUUUAUU motifs in the AU-rich elements of mRNAs. TTP binds Transportin-1 (Importin beta-2) which plays a role in shuttling TTP between P-bodies and stress granules.
R-HSA-450406 (Reactome) Phosphorylated BRF1 interacts with 14-3-3, becomes localized to the cytoskeleton, and no longer promotes RNA degradation. Phosphorylated BRF1 is, however, still able to bind RNA.
R-HSA-450422 (Reactome) KSRP (KHSRP) forms a complex with the PARN deadenylase, exosome components (3' to 5' mRNA decay), and the decapping enzyme DCP2. Tethering KSRP to a mRNA is sufficient to target the mRNA for degradation.
R-HSA-450431 (Reactome) TTP interacts directly with exonucleases (XRN1 and the exosome) and decapping enzymes (DCP1a and DCP2) which hydrolyze the mRNA bound by TTP. TTP also recruits PARN deadenylase, however a direct interaction between TTP and PARN has not been demonstrated.
R-HSA-450434 (Reactome) AUF1 monomers form dimers which bind the U-rich sequences in AU-rich elements of mRNAs. Binding of the mRNA causes the dimers of AUF1 to form tetramers. Nonphosphorylated AUF1 isoform p40 causes the mRNA to form a rigid structure whereas p40 that is phosphorylated at serines 83 and 87 does not. This difference may cause nonphosphorylated p40 to fail to destabilize the bound mRNA.
R-HSA-450463 (Reactome) TTP is phosphorylated by MK2 at serines 60 and 186.
R-HSA-450466 (Reactome) Ubiquitin-dependent proteolysis of AUF1 and nuclease-dependent destruction of AUF1-bound mRNA are coupled in an unknown way. It is possible that ubiquitinated AUF1 targets other members of the AUF1 and signal transduction regulated complex (ASTRC), such as polyA-binding protein, for degradation and this renders the mRNA susceptible to nucleases.
R-HSA-450474 (Reactome) MAPK-activated protein kinase 2 (MK2) phosphorylates BRF1 at serine 54, serine 92, serine 203, and an unknown site in the C terminus. Phosphorylation inhibits the ability of BRF1 to cause degradation of RNA. It is unknown if tetraphosphorylated BRF1 binds 14-3-3 in the same way as diphosphorylated BRF1 does.
R-HSA-450488 (Reactome) BRF1 recruits RNA degradation activities to hydrolyze the RNA bound to BRF1. Coimmunoprecipitation has shown BRF1 interacts with the exosome (3' to 5' nuclease), XRN1 (5' to 3' nuclease), and DCP1a and DCP2 (decapping). BRF1 localizes RNAs to processing bodies, sites of translation repression and possible sites of RNA degradation.
R-HSA-450490 (Reactome) BRF1 is phosphorylated at Serine92 and Serine203 by Protein kinase B/AKT. Protein kinase B is activated by phosphatidylinositol 3-kinase. Phosphorylation of BRF1 does not interfere with the ability of BRF1 to bind RNA or interact with enzymes that catalyze RNA degradation therefore larger complexes may contain phosphorylated BRF1.
R-HSA-450494 (Reactome) HuR binds AU-rich elements of mRNAs. Bound HuR can form oligomers on longer AU-rich elements. Phosphorylated HuR binds mRNA more tightly than unphosphorylated HuR does.
R-HSA-450499 (Reactome) KSRP is phosphorylated by activated protein kinase B/AKT at serine 193. Phosphorylation does not prevent KSRP from binding RNA.
R-HSA-450517 (Reactome) Butyrate response factor 1 (BRF1) binds AU-rich elements in the 3' untranslated region of mRNAs.
R-HSA-450533 (Reactome) Protein kinase C delta (PKCdelta) phosphorylates HuR (ELAVL1) at serine 221 and serine 318.
R-HSA-450550 (Reactome) Protein kinase C alpha (PKCalpha) phosphorylates HuR (ELAVL1) on serine221 and serine 158.
R-HSA-450551 (Reactome) Tetrameric AUF1 bound to RNA forms a complex with other proteins, including elongation factor eIF4G, polyA-binding protein PABP, Hsp, Hsc70, and Hsp27. AUF1 also directly interacts with polyadenylate.
R-HSA-450580 (Reactome) AUF1 is ubiquitinated at unknown sites. The number of ubiquitin molecules conjugated to AUF1 and their linkage is unknown. Ubiquitination is required for subsequent degradation of both AUF1 and the mRNA bound by AUF1. It is uncertain if AUF1 is in a larger complex when it is ubiquitinated.
R-HSA-450592 (Reactome) KSRP (KHSRP) binds AU-rich regions of target RNAs via its four K-homology (KH) domains.
R-HSA-450595 (Reactome) mRNA bound to HuR is exported from the nucleus by a mechanism that requires the shuttle protein APRIL but not pp32. Phosphorylation of APRIL determines its subcellular localization: APRIL phosphorylated at threonine244 is found in both the nucleus and cytoplasm while APRIL that is not phosphorylated at threonine244 is cytoplasmic.
HuR bound to mRNAs in the cytoplasm acts to stabilize the mRNAs by an unknown mechanism.
R-HSA-450620 (Reactome) KSRP phosphorylated at serine193 binds 14-3-3zeta (YWHAZ) which impairs the ability of KSRP to destabilize RNA. Thus the RNAs become stabilized. KSRP is able to shuttle between the nucleus and the cytoplasm. 14-3-3zeta is nucleoplasmic. Binding of KSRP to 14-3-3zeta causes KSRP to be retained in the nucleus.
R-HSA-451152 (Reactome) Activated MAPK p38 alpha and beta phosphorylate KSRP at threonine692. The phosphorylation interferes with the ability of KSRP to bind and destabilize RNA. Thus RNAs become stabilized.
R-HSA-482788 (Reactome) Phosphorylated BRF1 interacts with 14-3-3, becomes localized to the cytoskeleton, and no longer promotes RNA degradation. Phosphorylated BRF1 is, however, still able to bind RNA.
R-HSA-517674 (Reactome) HuR (ELAV1) phosphorylated on serine221 and serine158 binds COX-2 mRNA in the nucleus. The phosphorylation of serine 158 appears to affect RNA-binding while phosphorylation on serine 221 affects nucleocytoplasmic shuffling.
R-HSA-517705 (Reactome) HuR phosphorylated on ser221 and ser318 binds AU-rich regions of mRNAs. Phosphorylation on ser318 appears to affect RNA binding and phosphorylation of ser221 affects nucleocytoplasmic shuttling.
SETR-HSA-450387 (Reactome)
TNPO1R-HSA-450400 (Reactome)
TTP:mRNA ComplexArrowR-HSA-450400 (Reactome)
TTP:mRNA ComplexR-HSA-450431 (Reactome)
TTP:mRNA ComplexR-HSA-450463 (Reactome)
TTP:mRNA Degradation ComplexArrowR-HSA-450431 (Reactome)
UbR-HSA-450580 (Reactome)
Ubiquitinated AUF1

Tetramer: Destabilized mRNA

Complex		ArrowR-HSA-450580 (Reactome)
Ubiquitinated AUF1

Tetramer: Destabilized mRNA

Complex		R-HSA-450466 (Reactome)
XPO1R-HSA-450387 (Reactome)
XRN1R-HSA-450431 (Reactome)
XRN1R-HSA-450488 (Reactome)
YWHABR-HSA-450394 (Reactome)
YWHABR-HSA-450406 (Reactome)
YWHABR-HSA-482788 (Reactome)
YWHAZR-HSA-450620 (Reactome)
ZFP36L1R-HSA-450517 (Reactome)
ZFP36R-HSA-450400 (Reactome)
mRNA Transcript

Targeted by

AUF1(hnRNP D0)		R-HSA-450434 (Reactome)
mRNA Transcript

Targeted by

Tristetraproline		R-HSA-450400 (Reactome)
mRNA Transcript Targeted by BRF1R-HSA-450517 (Reactome)
mRNA Transcript

Targeted by HuR Phosphorylated on

Ser158 and Ser318.		R-HSA-517674 (Reactome)
mRNA Transcript

Targeted by HuR Phosphorylated on

Ser221 and Ser318		R-HSA-517705 (Reactome)
mRNA Transcript

Targeted by HuR with Unknown

Phosphorylation		R-HSA-450494 (Reactome)
mRNA Transcript Targeted by KSRPR-HSA-450592 (Reactome)
p-S158,S221-ELAVL1ArrowR-HSA-450550 (Reactome)
p-S158,S221-ELAVL1R-HSA-517674 (Reactome)
p-S193-KHSRPArrowR-HSA-450499 (Reactome)
p-S193-KHSRPR-HSA-450620 (Reactome)
p-S221,S318-ELAVL1ArrowR-HSA-450533 (Reactome)
p-S221,S318-ELAVL1R-HSA-517705 (Reactome)
p-S272,T222,T334-MAPKAPK2mim-catalysisR-HSA-450463 (Reactome)
p-S272,T222,T334-MAPKAPK2mim-catalysisR-HSA-450474 (Reactome)
p-T244-TNFSF13ArrowR-HSA-450595 (Reactome)
p-T244-TNFSF13R-HSA-450387 (Reactome)
p-T308,S473-AKT1mim-catalysisR-HSA-450490 (Reactome)
p-T308,S473-AKT1mim-catalysisR-HSA-450499 (Reactome)
p-T692-KHSRPArrowR-HSA-451152 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2733"
Personal tools