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

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9, 26, 44, 511, 6, 31, 6233, 402, 368, 12, 24, 284, 6, 31, 5711, 34, 55456315, 45, 47, 56455, 19, 28, 6031, 39, 523329, 36, 42, 53, 594, 13, 21, 22, 25...14, 16, 48, 50, 588, 24, 28, 347, 10, 12, 17-19, 27...2353, 23, 30, 43, 493511, 23, 5516, 48, 50, 5815, 47, 5615, 47cytosolnucleoplasmEXOSC7 EXOSC2 EXOSC6 HNRNPD-4 UBC(77-152) EXOSC2 p-T308,S473-AKT1EXOSC8 HSPA8 mRNA Transcript Targeted by HuR with Unknown Phosphorylation p-T180,Y182-MAPK14 PSMB1 p-S221,S318-ELAVL1 Exosome ComplexmRNA Transcript Targeted by BRF1 Phosphorylated BRF1(Ser54, Ser92,Ser203):mRNA:14-3-3ComplexPSME2 ZFP36L1 DIS3 mRNA TranscriptTargeted by HuRPhosphorylated onSer158 and Ser318.ATPAUF1 Dimer (isoformp37 or p40)p-S158,S221-ELAVL1 PSMD13 DCP2 DIS3 PhosphorylatedTTP:mRNA:14-3-3ComplexPARNPABPC1 p-T180,Y182-MAPK11 PSMB6 UBA52(1-76) UBB(77-152) KSRPPSMB8 PSMC2 UBC(229-304) PSMD6 SETp-S83,S87-Ub-HNRNPD-3 EXOSC4 ATPPSMC5 mRNA Transcript Targeted by BRF1 HuR:mRNA complexesEIF4G1EXOSC5 EXOSC1 p-S221,S318-ELAVL1EXOSC9 YWHAZPSMA1 TNPO1 UBC(153-228) EXOSC8 HSPB1 mRNA TranscriptTargeted byAUF1(hnRNP D0)CD83 mRNA 001 XPO1Phosphorylated KSRP(Ser193):14-3-3zetaComplexEXOSC7 EXOSC8 UBC(533-608) ELAVL1 HuR with UnknownPhosphorylation:mRNA ComplexHuRwithphosphoserine221andphosphoserine158:mRNA Complexp-S193-KHSRP Ub-HNRNPD-4 PSMB9 mRNA Transcript Targeted by KSRP ADPEXOSC2 AUF1 Complexed withTranslation andHeat Shock ProteinsmRNA Transcript Targeted by AUF1(hnRNP D0) mRNA Transcript Targeted by AUF1(hnRNP D0) SHFM1 Ubiquitinated AUF1Tetramer:Destabilized mRNAComplexEXOSC6 PSMF1 PSMA7 DCP2PSMA8 EXOSC8 p-S92,S203-ZFP36L1 mRNA Transcript Targeted by HuR with Unknown Phosphorylation PSMD7 mRNA TranscriptTargeted by HuRwith UnknownPhosphorylationUBC(305-380) p-S92,S203-ZFP36L1 HNRNPD-4 PSMD8 p-T244-TNFSF13 TNPO1PSME3 PSMD10 mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318 EXOSC9 DCP1Ap-S221,S318-ELAVL1 PSME4 PSMD9 mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 UbZFP36 DCP1A mRNA Transcript Targeted by BRF1 TNPO1 PSMD11 TNPO1 HSPB1HNRNPD-4 p-S83,S87-HNRNPD-3 DCP2 ATPHSPA1A Mg2+ PSMA6 PSMD4 Phosphorylated BRF1(Ser92,Ser203):mRNAComplexUBC(1-76) PSMB3 YWHAB HSPA8EXOSC1 UBB(1-76) PSMD2 KSRP mRNA TranscriptTargeted by HuRPhosphorylated onSer221 and Ser318EXOSC6 p-S193-KHSRPmRNA TranscriptTargeted by KSRPPSMD1 GPRC5A mRNA 001 mRNA Transcript Targeted by Tristetraproline p-S83,S87-HNRNPD-3 XRN1 DCP1A ELAVL1 mRNA Transcript Targeted by HuR with Unknown Phosphorylation mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 EXOSC6 BRF1:mRNADegradation ComplexPSMD3 EXOSC3 AUF1 Tetramer:Destabilized mRNAComplexELAVL1PSMD12 DCP2 EXOSC7 PSMD5 Phosphorylated BRF1(Ser92,Ser203):mRNA:14-3-3ComplexmRNA Transcript Targeted by KSRP KSRP:mRNA Complexp-T244-TNFSF13PSMB10 PSMC6 PRKCAZFP36L1EXOSC7 DIS3 EXOSC3 p-S158,S221-ELAVL1 YWHAB YWHABPSMB2 ADPPSME1 mRNA Transcript Targeted by Tristetraproline ANP32A UBC(609-684) HuRwithphosphoserine221andphosphoserine318:mRNA ComplexmRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318. HSPA1AELAVL1 DIS3 EXOSC4 HuR:APRIL:pp32:SET(SETalpha):Nup214(SETbeta):CRM1PSMB11 PSMB4 SET p-S158,S221-ELAVL1 HuR:mRNA ComplexEXOSC4 ENPP2 mRNA 001 EXOSC5 PSMA4 ZFP36L1 mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318. EXOSC3 p-T244-TNFSF13PABPC1PSMA5 mRNA Transcript Targeted by BRF1 PSMC1 YWHAB Phosphorylated BRF1(Ser54, Ser92,Ser203):mRNAComplexPhospho-MAP kinasep38 (Mg2+ cofactor)XRN1mRNA Transcript Targeted by HuR Phosphorylated on Ser158 and Ser318. p-T692-KHSRPEXOSC9 ZFP36 mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 p-S272,T222,T334-MAPKAPK2p-S60,S186-ZFP36 EXOSC3 RPS27A(1-76) ADPPSMA2 UBC(381-456) EIF4G1 PSMD14 mRNA Transcript Targeted by HuR Phosphorylated on Ser221 and Ser318 EXOSC5 UBC(457-532) p-S158,S221-ELAVL1NUP214mRNA Transcript Targeted by Tristetraproline EXOSC4 XPO1 ELAVL1 p-S54,S92,S203-p-ZFP36L1 UBB(153-228) mRNA Transcript Targeted by BRF1 TTP:mRNA DegradationComplexADPTNPO1 mRNA Transcript Targeted by AUF1(hnRNP D0) PSMC3 EXOSC1 BRF1:mRNA ComplexATPp-S83,S87-HNRNPD-3 PSMB7 EXOSC1 PRKCD(1-676)PARN mRNA TranscriptTargeted byTristetraprolineTTP:mRNA ComplexKSRP:mRNADegradation Complexp-S221,S318-ELAVL1 p-S54,S92,S203-p-ZFP36L1 26S proteasomePSMB5 mRNA Transcript Targeted by Tristetraproline YWHAZ ANP32APhosphorylatedTTP:mRNA Complexp-S221,S318-ELAVL1 EXOSC2 EXOSC9 EXOSC5 ZFP36mRNA TranscriptTargeted by BRF1PSMA3 NUP214 XRN1 PSMC4 KSRP p-S158,S221-ELAVL1 mRNA Transcript Targeted by BRF1 p-S60,S186-ZFP36 33, 4031, 4531, 4533, 402, 3612, 603635474, 6231, 4527, 6015, 45, 47644, 6233, 35, 402329, 36, 42, 5931, 457, 10, 18, 34, 38...647474713, 21, 22, 25, 37...31, 4531, 45314, 623533, 35, 4020, 643533, 406, 31354, 6239587, 10, 18, 34, 38...15, 476, 3119, 28, 607, 10, 18, 34, 38...3533, 358, 12, 24, 28, 6015, 474, 6229, 36, 42, 5931, 4533, 407, 10, 18, 34, 38...29, 36, 42, 593533, 4033, 405845


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: 64
Reactome Author 
Reactome Author: May, Bruce

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Ontology Terms

 

Bibliography

View all...
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  53. Gingerich TJ, Feige JJ, LaMarre J.; ''AU-rich elements and the control of gene expression through regulated mRNA stability.''; PubMed Europe PMC Scholia
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  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)
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