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

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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

External references

DataNodes

Name	Type	Database reference	Comment
26S proteasome	Complex	REACT_2353 (Reactome)
ADP	Metabolite	CHEBI:16761 (ChEBI)
ANP32A [nucleoplasm]	Protein	P39687 (Uniprot-TrEMBL)
ANP32A	Protein	P39687 (Uniprot-TrEMBL)
ATP	Metabolite	CHEBI:15422 (ChEBI)
AUF1 Complexed with Translation and Heat Shock Proteins	Complex	REACT_25605 (Reactome)
AUF1 Dimer (isoform p37 or p40)	Complex	REACT_25445 (Reactome)	Phosphorylated isoform p40 of AUF1 destabilizes mRNA. Isoform p37 (phosphorylation unknown) also destabilizes mRNA.
AUF1 Tetramer: Destabilized mRNA Complex	Complex	REACT_26524 (Reactome)
BRF1:mRNA Degradation Complex	Complex	REACT_25561 (Reactome)
BRF1:mRNA Complex	Complex	REACT_26687 (Reactome)
DCP1A [cytosol]	Protein	Q9NPI6 (Uniprot-TrEMBL)
DCP1A	Protein	Q9NPI6 (Uniprot-TrEMBL)
DCP2 [cytosol]	Protein	Q8IU60 (Uniprot-TrEMBL)
DCP2	Protein	Q8IU60 (Uniprot-TrEMBL)
DIS3 [cytosol]	Protein	Q9Y2L1 (Uniprot-TrEMBL)
EIF4G1 [cytosol]	Protein	Q04637 (Uniprot-TrEMBL)
EIF4G1	Protein	Q04637 (Uniprot-TrEMBL)
ELAVL1(1-326) [cytosol]	Protein	Q15717 (Uniprot-TrEMBL)
ELAVL1(1-326) [nucleoplasm]	Protein	Q15717 (Uniprot-TrEMBL)
ELAVL1(1-326)	Protein	Q15717 (Uniprot-TrEMBL)
EXOSC1 [cytosol]	Protein	Q9Y3B2 (Uniprot-TrEMBL)
EXOSC2 [cytosol]	Protein	Q13868 (Uniprot-TrEMBL)
EXOSC3 [cytosol]	Protein	Q9NQT5 (Uniprot-TrEMBL)
EXOSC4 [cytosol]	Protein	Q9NPD3 (Uniprot-TrEMBL)
EXOSC5 [cytosol]	Protein	Q9NQT4 (Uniprot-TrEMBL)
EXOSC6 [cytosol]	Protein	Q5RKV6 (Uniprot-TrEMBL)
EXOSC7 [cytosol]	Protein	Q15024 (Uniprot-TrEMBL)
EXOSC8 [cytosol]	Protein	Q96B26 (Uniprot-TrEMBL)
EXOSC9 [cytosol]	Protein	Q06265 (Uniprot-TrEMBL)
Exosome Complex	Complex	REACT_20841 (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.
HNRNPD-4 [cytosol]	Protein	Q14103-4 (Uniprot-TrEMBL)
HSPA1A(2-641) [cytosol]	Protein	P08107 (Uniprot-TrEMBL)
HSPA1A(2-641)	Protein	P08107 (Uniprot-TrEMBL)
HSPA8 [cytosol]	Protein	P11142 (Uniprot-TrEMBL)
HSPA8	Protein	P11142 (Uniprot-TrEMBL)
HSPB1 [cytosol]	Protein	P04792 (Uniprot-TrEMBL)
HSPB1	Protein	P04792 (Uniprot-TrEMBL)
HuR with phosphoserine221 and phosphoserine158:mRNA Complex	Complex	REACT_27037 (Reactome)
HuR with phosphoserine221 and phosphoserine318:mRNA Complex	Complex	REACT_25770 (Reactome)
HuR with Unknown Phosphorylation: mRNA Complex	Complex	REACT_26059 (Reactome)
HuR:APRIL:pp32:SET/SETalpha:Nup214/SETbeta:CRM1 Complex	Complex	REACT_25847 (Reactome)
HuR:mRNA Complex	Complex	REACT_25608 (Reactome)
HuR:mRNA Complexes	Complex	REACT_26913 (Reactome)
KHSRP(1-710) [cytosol]	Protein	Q92945 (Uniprot-TrEMBL)
KHSRP(1-710)	Protein	Q92945 (Uniprot-TrEMBL)
KSRP:mRNA Degradation Complex	Complex	REACT_26058 (Reactome)
KSRP:mRNA Complex	Complex	REACT_26697 (Reactome)
Mg2+ [cytosol]	Metabolite	CHEBI:18420 (ChEBI)
NUP214 [nucleoplasm]	Protein	P35658 (Uniprot-TrEMBL)
NUP214	Protein	P35658 (Uniprot-TrEMBL)
PABPC1 [cytosol]	Protein	P11940 (Uniprot-TrEMBL)
PABPC1	Protein	P11940 (Uniprot-TrEMBL)
PARN [cytosol]	Protein	O95453 (Uniprot-TrEMBL)
PARN	Protein	O95453 (Uniprot-TrEMBL)
PRKCA	Protein	P17252 (Uniprot-TrEMBL)
PRKCD(1-676)	Protein	Q05655 (Uniprot-TrEMBL)
PSMA1 [cytosol]	Protein	P25786 (Uniprot-TrEMBL)
PSMA2 [cytosol]	Protein	P25787 (Uniprot-TrEMBL)
PSMA3 [cytosol]	Protein	P25788 (Uniprot-TrEMBL)
PSMA4 [cytosol]	Protein	P25789 (Uniprot-TrEMBL)
PSMA5 [cytosol]	Protein	P28066 (Uniprot-TrEMBL)
PSMA6 [cytosol]	Protein	P60900 (Uniprot-TrEMBL)
PSMA7(2-248) [cytosol]	Protein	O14818 (Uniprot-TrEMBL)
PSMA8 [cytosol]	Protein	Q8TAA3 (Uniprot-TrEMBL)
PSMB1 [cytosol]	Protein	P20618 (Uniprot-TrEMBL)
PSMB10 [cytosol]	Protein	P40306 (Uniprot-TrEMBL)
PSMB11 [cytosol]	Protein	A5LHX3 (Uniprot-TrEMBL)
PSMB2 [cytosol]	Protein	P49721 (Uniprot-TrEMBL)
PSMB3 [cytosol]	Protein	P49720 (Uniprot-TrEMBL)
PSMB4 [cytosol]	Protein	P28070 (Uniprot-TrEMBL)
PSMB5 [cytosol]	Protein	P28074 (Uniprot-TrEMBL)
PSMB6 [cytosol]	Protein	P28072 (Uniprot-TrEMBL)
PSMB7 [cytosol]	Protein	Q99436 (Uniprot-TrEMBL)
PSMB8 [cytosol]	Protein	P28062 (Uniprot-TrEMBL)
PSMB9 [cytosol]	Protein	P28065 (Uniprot-TrEMBL)
PSMC1(2-440) [cytosol]	Protein	P62191 (Uniprot-TrEMBL)
PSMC2 [cytosol]	Protein	P35998 (Uniprot-TrEMBL)
PSMC3 [cytosol]	Protein	P17980 (Uniprot-TrEMBL)
PSMC4 [cytosol]	Protein	P43686 (Uniprot-TrEMBL)
PSMC5 [cytosol]	Protein	P62195 (Uniprot-TrEMBL)
PSMC6(2-389) [cytosol]	Protein	P62333 (Uniprot-TrEMBL)
PSMD1 [cytosol]	Protein	Q99460 (Uniprot-TrEMBL)
PSMD10 [cytosol]	Protein	O75832 (Uniprot-TrEMBL)
PSMD11 [cytosol]	Protein	O00231 (Uniprot-TrEMBL)
PSMD12 [cytosol]	Protein	O00232 (Uniprot-TrEMBL)
PSMD13 [cytosol]	Protein	Q9UNM6 (Uniprot-TrEMBL)
PSMD14 [cytosol]	Protein	O00487 (Uniprot-TrEMBL)
PSMD2 [cytosol]	Protein	Q13200 (Uniprot-TrEMBL)
PSMD3 [cytosol]	Protein	O43242 (Uniprot-TrEMBL)
PSMD4(2-377) [cytosol]	Protein	P55036 (Uniprot-TrEMBL)
PSMD5 [cytosol]	Protein	Q16401 (Uniprot-TrEMBL)
PSMD6(2-389) [cytosol]	Protein	Q15008 (Uniprot-TrEMBL)
PSMD7(2-324) [cytosol]	Protein	P51665 (Uniprot-TrEMBL)
PSMD8 [cytosol]	Protein	P48556 (Uniprot-TrEMBL)
PSMD9 [cytosol]	Protein	O00233 (Uniprot-TrEMBL)
PSME1 [cytosol]	Protein	Q06323 (Uniprot-TrEMBL)
PSME2 [cytosol]	Protein	Q9UL46 (Uniprot-TrEMBL)
PSME3 [cytosol]	Protein	P61289 (Uniprot-TrEMBL)
PSME4 [cytosol]	Protein	Q14997 (Uniprot-TrEMBL)
PSMF1(2-271) [cytosol]	Protein	Q92530 (Uniprot-TrEMBL)
Phospho-MAP kinase p38 (Mg2+ cofactor)	Complex	REACT_12273 (Reactome)
Phosphorylated TTP:mRNA Complex	Complex	REACT_25681 (Reactome)
Phosphorylated TTP:mRNA:14-3-3 Complex	Complex	REACT_25699 (Reactome)
Phosphorylated BRF1 (Ser54, Ser92, Ser203):mRNA Complex	Complex	REACT_25904 (Reactome)
Phosphorylated BRF1 (Ser54, Ser92, Ser203):mRNA:14-3-3 Complex	Complex	REACT_25856 (Reactome)
Phosphorylated BRF1 (Ser92, Ser203):mRNA:14-3-3 Complex	Complex	REACT_26426 (Reactome)
Phosphorylated BRF1 (Ser92, Ser203):mRNA Complex	Complex	REACT_25600 (Reactome)
Phosphorylated KSRP (Ser193):14-3-3zeta Complex	Complex	REACT_26013 (Reactome)
SET(1-290) [nucleoplasm]	Protein	Q01105 (Uniprot-TrEMBL)
SET(1-290)	Protein	Q01105 (Uniprot-TrEMBL)
TNPO1 [cytosol]	Protein	Q92973 (Uniprot-TrEMBL)
TNPO1	Protein	Q92973 (Uniprot-TrEMBL)
TTP:mRNA Complex	Complex	REACT_26727 (Reactome)
TTP:mRNA Degradation Complex	Complex	REACT_25473 (Reactome)
Ub-HNRNPD-4 [cytosol]	Protein	Q14103-4 (Uniprot-TrEMBL)
Ub	Protein	REACT_3316 (Reactome)
Ubiquitinated AUF1 Tetramer: Destabilized mRNA Complex	Complex	REACT_26356 (Reactome)
XPO1 [nucleoplasm]	Protein	O14980 (Uniprot-TrEMBL)
XPO1	Protein	O14980 (Uniprot-TrEMBL)
XRN1 [cytosol]	Protein	Q8IZH2 (Uniprot-TrEMBL)
XRN1	Protein	Q8IZH2 (Uniprot-TrEMBL)
YWHAB(1-246) [cytosol]	Protein	P31946 (Uniprot-TrEMBL)
YWHAB(1-246)	Protein	P31946 (Uniprot-TrEMBL)
YWHAZ [nucleoplasm]	Protein	P63104 (Uniprot-TrEMBL)
YWHAZ	Protein	P63104 (Uniprot-TrEMBL)
ZFP36 [cytosol]	Protein	P26651 (Uniprot-TrEMBL)
ZFP36L1 [cytosol]	Protein	Q07352 (Uniprot-TrEMBL)
ZFP36L1	Protein	Q07352 (Uniprot-TrEMBL)
ZFP36	Protein	P26651 (Uniprot-TrEMBL)
mRNA Transcript Targeted by AUF1(hnRNP D0)		REACT_27038 (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		REACT_26157 (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 BRF1		REACT_26387 (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.		REACT_26315 (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		REACT_26577 (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		REACT_27075 (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		REACT_27068 (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.
p-S158,S221-ELAVL1(1-326) [cytosol]	Protein	Q15717 (Uniprot-TrEMBL)
p-S158,S221-ELAVL1(1-326) [nucleoplasm]	Protein	Q15717 (Uniprot-TrEMBL)
p-S158,S221-ELAVL1(1-326)	Protein	Q15717 (Uniprot-TrEMBL)
p-S193-KHSRP(1-710) [nucleoplasm]	Protein	Q92945 (Uniprot-TrEMBL)
p-S193-KHSRP(1-710)	Protein	Q92945 (Uniprot-TrEMBL)
p-S221,S318-ELAVL1(1-326) [cytosol]	Protein	Q15717 (Uniprot-TrEMBL)
p-S221,S318-ELAVL1(1-326) [nucleoplasm]	Protein	Q15717 (Uniprot-TrEMBL)
p-S221,S318-ELAVL1(1-326)	Protein	Q15717 (Uniprot-TrEMBL)
p-S54,S92,S203-p-ZFP36L1 [cytosol]	Protein	Q07352 (Uniprot-TrEMBL)
p-S60,S186-ZFP36 [cytosol]	Protein	P26651 (Uniprot-TrEMBL)
p-S83,S87-HNRNPD-3 [cytosol]	Protein	Q14103-3 (Uniprot-TrEMBL)
p-S83,S87-Ub-HNRNPD-3 [cytosol]	Protein	Q14103-3 (Uniprot-TrEMBL)
p-S92,S203-ZFP36L1 [cytosol]	Protein	Q07352 (Uniprot-TrEMBL)
p-T180,Y182-MAPK11 [cytosol]	Protein	Q15759 (Uniprot-TrEMBL)
p-T180,Y182-MAPK14 [cytosol]	Protein	Q16539 (Uniprot-TrEMBL)
p-T222,S272,T334-MAPKAPK2	Protein	P49137 (Uniprot-TrEMBL)
p-T244-TNFSF13 [nucleoplasm]	Protein	O75888 (Uniprot-TrEMBL)
p-T244-TNFSF13	Protein	O75888 (Uniprot-TrEMBL)
p-T308,S473-AKT1	Protein	P31749 (Uniprot-TrEMBL)
p-T692-KHSRP(1-710)	Protein	Q92945 (Uniprot-TrEMBL)

Annotated Interactions

Source	Target	Type	Database reference	Comment
26S proteasome		mim-catalysis	REACT_25343 (Reactome)
	ADP	Arrow	REACT_24965 (Reactome)
	ADP	Arrow	REACT_25016 (Reactome)
	ADP	Arrow	REACT_25171 (Reactome)
	ADP	Arrow	REACT_25187 (Reactome)
	ADP	Arrow	REACT_25202 (Reactome)
	ADP	Arrow	REACT_25285 (Reactome)
	ADP	Arrow	REACT_25335 (Reactome)
ANP32A			REACT_25286 (Reactome)
ATP			REACT_24965 (Reactome)
ATP			REACT_25016 (Reactome)
ATP			REACT_25171 (Reactome)
ATP			REACT_25187 (Reactome)
ATP			REACT_25202 (Reactome)
ATP			REACT_25285 (Reactome)
ATP			REACT_25335 (Reactome)
	AUF1 Complexed with Translation and Heat Shock Proteins	Arrow	REACT_25267 (Reactome)
AUF1 Complexed with Translation and Heat Shock Proteins			REACT_25315 (Reactome)
AUF1 Dimer (isoform p37 or p40)			REACT_24997 (Reactome)
	AUF1 Tetramer: Destabilized mRNA Complex	Arrow	REACT_24997 (Reactome)
AUF1 Tetramer: Destabilized mRNA Complex			REACT_25267 (Reactome)
	BRF1:mRNA Degradation Complex	Arrow	REACT_25265 (Reactome)
	BRF1:mRNA Complex	Arrow	REACT_25293 (Reactome)
BRF1:mRNA Complex			REACT_25265 (Reactome)
BRF1:mRNA Complex			REACT_25285 (Reactome)
BRF1:mRNA Complex			REACT_25335 (Reactome)
DCP1A			REACT_25265 (Reactome)
DCP1A			REACT_25297 (Reactome)
DCP2			REACT_25257 (Reactome)
DCP2			REACT_25265 (Reactome)
DCP2			REACT_25297 (Reactome)
EIF4G1			REACT_25267 (Reactome)
ELAVL1(1-326)			REACT_25016 (Reactome)
ELAVL1(1-326)			REACT_25067 (Reactome)
ELAVL1(1-326)			REACT_25202 (Reactome)
Exosome Complex			REACT_25257 (Reactome)
Exosome Complex			REACT_25265 (Reactome)
Exosome Complex			REACT_25297 (Reactome)
HSPA1A(2-641)			REACT_25267 (Reactome)
HSPA8			REACT_25267 (Reactome)
HSPB1			REACT_25267 (Reactome)
	HuR with phosphoserine221 and phosphoserine158:mRNA Complex	Arrow	REACT_24962 (Reactome)
	HuR with phosphoserine221 and phosphoserine318:mRNA Complex	Arrow	REACT_24973 (Reactome)
	HuR with Unknown Phosphorylation: mRNA Complex	Arrow	REACT_25067 (Reactome)
	HuR:APRIL:pp32:SET/SETalpha:Nup214/SETbeta:CRM1 Complex	Arrow	REACT_25286 (Reactome)
HuR:APRIL:pp32:SET/SETalpha:Nup214/SETbeta:CRM1 Complex			REACT_24924 (Reactome)
	HuR:mRNA Complex	Arrow	REACT_24924 (Reactome)
HuR:mRNA Complexes			REACT_25286 (Reactome)
KHSRP(1-710)			REACT_24965 (Reactome)
KHSRP(1-710)			REACT_25187 (Reactome)
KHSRP(1-710)			REACT_25230 (Reactome)
	KSRP:mRNA Degradation Complex	Arrow	REACT_25257 (Reactome)
	KSRP:mRNA Complex	Arrow	REACT_25230 (Reactome)
KSRP:mRNA Complex			REACT_25257 (Reactome)
NUP214			REACT_25286 (Reactome)
PABPC1			REACT_25267 (Reactome)
PARN			REACT_25257 (Reactome)
PRKCA		mim-catalysis	REACT_25016 (Reactome)
PRKCD(1-676)		mim-catalysis	REACT_25202 (Reactome)
Phospho-MAP kinase p38 (Mg2+ cofactor)		mim-catalysis	REACT_24965 (Reactome)
	Phosphorylated TTP:mRNA Complex	Arrow	REACT_25171 (Reactome)
Phosphorylated TTP:mRNA Complex			REACT_24978 (Reactome)
	Phosphorylated TTP:mRNA:14-3-3 Complex	Arrow	REACT_24978 (Reactome)
	Phosphorylated BRF1 (Ser54, Ser92, Ser203):mRNA Complex	Arrow	REACT_25285 (Reactome)
Phosphorylated BRF1 (Ser54, Ser92, Ser203):mRNA Complex			REACT_25272 (Reactome)
	Phosphorylated BRF1 (Ser54, Ser92, Ser203):mRNA:14-3-3 Complex	Arrow	REACT_25272 (Reactome)
	Phosphorylated BRF1 (Ser92, Ser203):mRNA:14-3-3 Complex	Arrow	REACT_24951 (Reactome)
	Phosphorylated BRF1 (Ser92, Ser203):mRNA Complex	Arrow	REACT_25335 (Reactome)
Phosphorylated BRF1 (Ser92, Ser203):mRNA Complex			REACT_24951 (Reactome)
	Phosphorylated KSRP (Ser193):14-3-3zeta Complex	Arrow	REACT_25152 (Reactome)
			REACT_24924 (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.
			REACT_24951 (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.
			REACT_24962 (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.
			REACT_24965 (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.
			REACT_24973 (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.
			REACT_24978 (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.
			REACT_24997 (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.
			REACT_25016 (Reactome)	Protein kinase C alpha (PKCalpha) phosphorylates HuR (ELAVL1) on serine221 and serine 158.
			REACT_25067 (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.
			REACT_25152 (Reactome)	KSRP phosphorylated at serine193 binds 14-3-3zeta 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.
			REACT_25171 (Reactome)	TTP is phosphorylated by MK2 at serines 60 and 186.
			REACT_25187 (Reactome)	KSRP is phosphorylated by activated protein kinase B/AKT at serine 193. Phosphorylation does not prevent KSRP from binding RNA.
			REACT_25202 (Reactome)	Protein kinase C delta (PKCdelta) phosphorylates HuR (ELAVL1) at serine 221 and serine 318.
			REACT_25230 (Reactome)	KSRP (KHSRP) binds AU-rich regions of target RNAs via its four K-homology (KH) domains.
			REACT_25257 (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.
			REACT_25265 (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.
			REACT_25267 (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.
			REACT_25272 (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.
			REACT_25285 (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.
			REACT_25286 (Reactome)	HuR interacts with SETalpha (Template activating factor 1), SETbeta (CAN/Nup214), APRIL, pp32, and the nuclear export factor CRM1.
			REACT_25293 (Reactome)	Butyrate response factor 1 (BRF1) binds AU-rich elements in the 3' untranslated region of mRNAs.
			REACT_25297 (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.
			REACT_25315 (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.
			REACT_25335 (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.
			REACT_25343 (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.
			REACT_25366 (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.
SET(1-290)			REACT_25286 (Reactome)
TNPO1			REACT_25366 (Reactome)
	TTP:mRNA Complex	Arrow	REACT_25366 (Reactome)
TTP:mRNA Complex			REACT_25171 (Reactome)
TTP:mRNA Complex			REACT_25297 (Reactome)
	TTP:mRNA Degradation Complex	Arrow	REACT_25297 (Reactome)
Ub			REACT_25315 (Reactome)
	Ubiquitinated AUF1 Tetramer: Destabilized mRNA Complex	Arrow	REACT_25315 (Reactome)
Ubiquitinated AUF1 Tetramer: Destabilized mRNA Complex			REACT_25343 (Reactome)
XPO1			REACT_25286 (Reactome)
XRN1			REACT_25265 (Reactome)
XRN1			REACT_25297 (Reactome)
YWHAB(1-246)			REACT_24951 (Reactome)
YWHAB(1-246)			REACT_24978 (Reactome)
YWHAB(1-246)			REACT_25272 (Reactome)
YWHAZ			REACT_25152 (Reactome)
ZFP36L1			REACT_25293 (Reactome)
ZFP36			REACT_25366 (Reactome)
mRNA Transcript Targeted by AUF1(hnRNP D0)			REACT_24997 (Reactome)
mRNA Transcript Targeted by Tristetraproline			REACT_25366 (Reactome)
mRNA Transcript Targeted by BRF1			REACT_25293 (Reactome)
mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318.			REACT_24962 (Reactome)
mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318			REACT_24973 (Reactome)
mRNA Transcript Targeted by HuR with Unknown Phosphorylation			REACT_25067 (Reactome)
mRNA Transcript Targeted by KSRP			REACT_25230 (Reactome)
	p-S158,S221-ELAVL1(1-326)	Arrow	REACT_25016 (Reactome)
p-S158,S221-ELAVL1(1-326)			REACT_24962 (Reactome)
	p-S193-KHSRP(1-710)	Arrow	REACT_25187 (Reactome)
p-S193-KHSRP(1-710)			REACT_25152 (Reactome)
	p-S221,S318-ELAVL1(1-326)	Arrow	REACT_25202 (Reactome)
p-S221,S318-ELAVL1(1-326)			REACT_24973 (Reactome)
p-T222,S272,T334-MAPKAPK2		mim-catalysis	REACT_25171 (Reactome)
p-T222,S272,T334-MAPKAPK2		mim-catalysis	REACT_25285 (Reactome)
	p-T244-TNFSF13	Arrow	REACT_24924 (Reactome)
p-T244-TNFSF13			REACT_25286 (Reactome)
p-T308,S473-AKT1		mim-catalysis	REACT_25187 (Reactome)
p-T308,S473-AKT1		mim-catalysis	REACT_25335 (Reactome)
	p-T692-KHSRP(1-710)	Arrow	REACT_24965 (Reactome)