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

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4, 11, 12, 553019, 23, 34, 639, 24, 35, 45, 575019, 23, 33, 6346, 5013, 623, 10, 5315, 54, 56449, 35, 45, 577, 23, 32, 378, 13, 17, 48, 59293, 28, 31, 5215, 44, 54, 5616, 21, 51, 61, 6515, 5422, 33, 422, 5, 6, 25, 31...3, 14, 25, 2844296216, 22, 421, 14, 18, 20, 26...nucleoplasmcytosolmRNA TranscriptTargeted by HuRPhosphorylated onSer221 and Ser318YWHAB mRNA Transcript Targeted by BRF1 mRNA Transcript Targeted by AUF1(hnRNP D0) mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318. mRNA Transcript Targeted by AUF1(hnRNP D0) mRNA Transcript Targeted by BRF1 p-S221,S318-ELAVL1 EXOSC4 mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318 p-S193-KHSRPXRN1TNPO1 p-S83,S87-HNRNPD-3 mRNA TranscriptTargeted by BRF1PABPC1 Phospho-MAP kinasep38 (Mg2+ cofactor)KSRP DIS3 PSME3 HSPB1 AUF1 Tetramer:Destabilized mRNAComplexEXOSC2 EXOSC1 PSMD1 PSMD9 PSMD10 UBC(457-532) p-T180,Y182-MAPK11 PhosphorylatedTTP:mRNA:14-3-3Complexp-T308,S473-AKT1UBB(77-152) EXOSC1 EXOSC3 PSMB1 p-S221,S318-ELAVL1ZFP36L1 PSME2 mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318. mRNA Transcript Targeted by KSRP p-S272,T222,T334-MAPKAPK2HNRNPD-4 HuR:APRIL:pp32:SET(SETalpha):Nup214(SETbeta):CRM1PSMC2 PSMD3 PSMA7 UBC(533-608) PSMA1 mRNA Transcript Targeted by HuR with Unknown Phosphorylation ATPPSMB4 mRNA TranscriptTargeted byTristetraprolineTTP:mRNA DegradationComplexPSMD14 ELAVL1 PSMB8 TNPO1p-S221,S318-ELAVL1 KSRP:mRNA ComplexXPO1mRNA Transcript Targeted by HuR with Unknown Phosphorylation ANP32A p-S83,S87-HNRNPD-3 PSMC3 p-S83,S87-HNRNPD-3 p-S158,S221-ELAVL1 HNRNPD-4 HuR with UnknownPhosphorylation:mRNA ComplexHuR:mRNA complexesCD83 mRNA 001 HuRwithphosphoserine221andphosphoserine158:mRNA ComplexEXOSC4 PSMD12 ADPDCP1A EXOSC4 mRNA Transcript Targeted by BRF1 YWHAZEXOSC1 UBB(1-76) PSMD5 EXOSC5 p-S221,S318-ELAVL1 ATPp-T180,Y182-MAPK14 mRNA Transcript Targeted by HuR with Unknown Phosphorylation AUF1 Complexed withTranslation andHeat Shock ProteinsZFP36L1 PSME4 mRNA Transcript Targeted by Tristetraproline Phosphorylated BRF1(Ser92,Ser203):mRNA:14-3-3ComplexTNPO1 p-S158,S221-ELAVL1 EXOSC5 ANP32APSMB6 mRNA Transcript Targeted by KSRP UBC(229-304) PSMA8 EXOSC2 PSMF1 PSMB10 NUP214 PhosphorylatedTTP:mRNA ComplexEXOSC8 UBB(153-228) UBC(1-76) PARN PSMB11 PSMD6 DCP1Ap-S54,S92,S203-p-ZFP36L1 Phosphorylated BRF1(Ser54, Ser92,Ser203):mRNAComplexp-S92,S203-ZFP36L1 ZFP36L1PSMB7 EIF4G1ELAVL1 mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318. EXOSC4 p-S60,S186-ZFP36 HNRNPD-4 DIS3 mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 ZFP36ZFP36 Exosome Complexp-S158,S221-ELAVL1 PSMD7 HSPA8Mg2+ ADPDCP2 ELAVL1EXOSC3 HuRwithphosphoserine221andphosphoserine318:mRNA Complexp-T244-TNFSF13ENPP2 mRNA 001 EXOSC9 p-S54,S92,S203-p-ZFP36L1 p-T244-TNFSF13PSMC5 mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 SET EXOSC8 PSMB5 ATPUBC(305-380) mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 p-S158,S221-ELAVL1Phosphorylated BRF1(Ser54, Ser92,Ser203):mRNA:14-3-3ComplexKSRP PSMD11 mRNA Transcript Targeted by BRF1 DCP2 EXOSC3 mRNA Transcript Targeted by Tristetraproline PRKCAmRNA TranscriptTargeted byAUF1(hnRNP D0)EXOSC8 SHFM1 EXOSC6 EXOSC6 ZFP36 PSMD8 EXOSC6 GPRC5A mRNA 001 PSMB9 AUF1 Dimer (isoformp37 or p40)ELAVL1 ELAVL1 EXOSC9 UBC(77-152) UbADPEXOSC9 mRNA TranscriptTargeted by KSRPEXOSC5 EXOSC3 PSME1 EXOSC9 p-S158,S221-ELAVL1 mRNA Transcript Targeted by Tristetraproline PSMA3 mRNA TranscriptTargeted by HuRwith UnknownPhosphorylationXRN1 EXOSC7 mRNA TranscriptTargeted by HuRPhosphorylated onSer158 and Ser318.EIF4G1 PABPC1TNPO1 p-S60,S186-ZFP36 EXOSC7 BRF1:mRNADegradation ComplexKSRP:mRNADegradation ComplexDCP2EXOSC8 DCP1A PARNPSMC4 EXOSC7 XRN1 mRNA Transcript Targeted by AUF1(hnRNP D0) YWHAB EXOSC6 EXOSC1 ATPYWHABmRNA Transcript Targeted by BRF1 p-S193-KHSRP ADPPhosphorylated BRF1(Ser92,Ser203):mRNAComplex26S proteasomeNUP214mRNA Transcript Targeted by BRF1 p-T244-TNFSF13 PSMD13 HuR:mRNA ComplexBRF1:mRNA ComplexPSMC6 RPS27A(1-76) EXOSC2 UBC(609-684) UBC(153-228) EXOSC7 PSMC1 DCP2 p-S221,S318-ELAVL1 KSRPDIS3 Ubiquitinated AUF1Tetramer:Destabilized mRNAComplexmRNA Transcript Targeted by Tristetraproline HSPA1AHSPA8 PRKCD(1-676)PSMD2 PSMB2 HSPA1A EXOSC2 DIS3 YWHAZ SETPSMA6 p-S83,S87-Ub-HNRNPD-3 UBA52(1-76) Phosphorylated KSRP(Ser193):14-3-3zetaComplexHSPB1PSMA2 EXOSC5 YWHAB XPO1 UBC(381-456) PSMA4 TNPO1 PSMA5 p-S92,S203-ZFP36L1 Ub-HNRNPD-4 PSMB3 PSMD4 TTP:mRNA ComplexmRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 p-T692-KHSRP3, 442918, 33, 39, 40, 58...133, 2815, 5425, 3129, 502946, 503646, 5018, 33, 39, 40, 58...351623, 32, 373, 282, 6, 38, 41, 47...25, 313, 4453298, 13, 48, 5928293, 443, 4415, 44, 5446, 508, 13, 48, 5946, 503, 4432, 34158, 13, 48, 5913, 6215, 5427, 3625, 312929, 46, 5025, 3146, 503, 443518, 33, 39, 40, 58...346, 50442925, 311518, 33, 39, 40, 58...1526, 3229, 46, 503, 4419, 23, 32, 34, 6315


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: 66
Reactome Author 
Reactome Author: May, Bruce

Quality Tags

Ontology Terms

 

Bibliography

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  44. 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
  45. 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
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  48. 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
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  52. 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
  53. 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
  54. 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
  55. Barreau C, Paillard L, Osborne HB.; ''AU-rich elements and associated factors: are there unifying principles?''; PubMed Europe PMC
  56. 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
  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
  58. 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
  59. 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
  60. 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
  61. 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
  62. 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
  63. Laroia G, Schneider RJ.; ''Alternate exon insertion controls selective ubiquitination and degradation of different AUF1 protein isoforms.''; PubMed Europe PMC
  64. Chang WL, Tarn WY.; ''A role for transportin in deposition of TTP to cytoplasmic RNA granules and mRNA decay.''; PubMed Europe PMC
  65. 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

History

View all...
CompareRevisionActionTimeUserComment
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

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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)
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