ATF4 activates genes (Homo sapiens)

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3, 7, 8, 12-14, 16...138-11, 1312146, 16317cytosolendoplasmic reticulum lumennucleoplasmEXOSC4 EXOSC3 ATF4IGFBP1NF-YmRNA Transcript Targeted by KSRP ATF3DIS3 EXOSC2 ATF3 geneEXOSC9 HERPUD1 geneASNSASNS geneNFYA EXOSC7 IL8 geneCCL2 geneKSRP:mRNADegradation ComplexEXOSC1 EXOSC5 NFYC DDIT3HERPUD1CCL2ATF6(1-380)NFYB DDIT3 genePARN IL8EXOSC6 IGFPB1 geneDCP2 KSRP EXOSC8 21, 4, 5, 15


ATF4 is a transcription factor and activates expression of IL-8, MCP1, IGFBP-1, CHOP, HERP1 and ATF3. View original pathway at:Reactome.


Pathway is converted from Reactome ID: 380994
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce

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  1. 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
  2. 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
  3. Marchand A, Tomkiewicz C, Magne L, Barouki R, Garlatti M.; ''Endoplasmic reticulum stress induction of insulin-like growth factor-binding protein-1 involves ATF4.''; PubMed Europe PMC
  4. 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
  5. 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
  6. Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M, Mori K.; ''ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response.''; PubMed Europe PMC
  7. Yamaguchi Y, Larkin D, Lara-Lemus R, Ramos-CastaƱeda J, Liu M, Arvan P.; ''Endoplasmic reticulum (ER) chaperone regulation and survival of cells compensating for deficiency in the ER stress response kinase, PERK.''; PubMed Europe PMC
  8. Gargalovic PS, Imura M, Zhang B, Gharavi NM, Clark MJ, Pagnon J, Yang WP, He A, Truong A, Patel S, Nelson SF, Horvath S, Berliner JA, Kirchgessner TG, Lusis AJ.; ''Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids.''; PubMed Europe PMC
  9. Mukaida N, Shiroo M, Matsushima K.; ''Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8.''; PubMed Europe PMC
  10. Matsushima K, Morishita K, Yoshimura T, Lavu S, Kobayashi Y, Lew W, Appella E, Kung HF, Leonard EJ, Oppenheim JJ.; ''Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor.''; PubMed Europe PMC
  11. Kowalski J, Denhardt DT.; ''Regulation of the mRNA for monocyte-derived neutrophil-activating peptide in differentiating HL60 promyelocytes.''; PubMed Europe PMC
  12. Ma Y, Hendershot LM.; ''Herp is dually regulated by both the endoplasmic reticulum stress-specific branch of the unfolded protein response and a branch that is shared with other cellular stress pathways.''; PubMed Europe PMC
  13. Gargalovic PS, Gharavi NM, Clark MJ, Pagnon J, Yang WP, He A, Truong A, Baruch-Oren T, Berliner JA, Kirchgessner TG, Lusis AJ.; ''The unfolded protein response is an important regulator of inflammatory genes in endothelial cells.''; PubMed Europe PMC
  14. Gjymishka A, Su N, Kilberg MS.; ''Transcriptional induction of the human asparagine synthetase gene during the unfolded protein response does not require the ATF6 and IRE1/XBP1 arms of the pathway.''; PubMed Europe PMC
  15. 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
  16. Averous J, Bruhat A, Jousse C, Carraro V, Thiel G, Fafournoux P.; ''Induction of CHOP expression by amino acid limitation requires both ATF4 expression and ATF2 phosphorylation.''; PubMed Europe PMC
  17. Armstrong JL, Flockhart R, Veal GJ, Lovat PE, Redfern CP.; ''Regulation of endoplasmic reticulum stress-induced cell death by ATF4 in neuroectodermal tumor cells.''; PubMed Europe PMC


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101302view11:19, 1 November 2018ReactomeTeamreactome version 66
100839view20:50, 31 October 2018ReactomeTeamreactome version 65
100380view19:24, 31 October 2018ReactomeTeamreactome version 64
99927view16:08, 31 October 2018ReactomeTeamreactome version 63
99482view14:40, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99135view12:40, 31 October 2018ReactomeTeamreactome version 62
93981view13:49, 16 August 2017ReactomeTeamreactome version 61
93583view11:28, 9 August 2017ReactomeTeamreactome version 61
87088view14:26, 18 July 2016MkutmonOntology Term : 'transcription pathway' added !
87087view14:25, 18 July 2016MkutmonOntology Term : 'PW:0001756' removed !
87086view14:25, 18 July 2016MkutmonOntology Term : 'peptide and protein metabolic process' added !
86689view09:24, 11 July 2016ReactomeTeamreactome version 56
83046view09:46, 18 November 2015ReactomeTeamVersion54
81769view10:15, 26 August 2015ReactomeTeamVersion53
76999view08:29, 17 July 2014ReactomeTeamFixed remaining interactions
76704view12:07, 16 July 2014ReactomeTeamFixed remaining interactions
76030view10:09, 11 June 2014ReactomeTeamRe-fixing comment source
75739view11:22, 10 June 2014ReactomeTeamReactome 48 Update
75089view14:04, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74736view08:49, 30 April 2014ReactomeTeamNew pathway

External references


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NameTypeDatabase referenceComment
ASNS geneGeneProductENSG00000070669 (Ensembl)
ASNSProteinP08243 (Uniprot-TrEMBL)
ATF3 geneGeneProductENSG00000162772 (Ensembl)
ATF3ProteinP18847 (Uniprot-TrEMBL)
ATF4ProteinP18848 (Uniprot-TrEMBL)
ATF6(1-380)ProteinP18850 (Uniprot-TrEMBL)
CCL2 geneGeneProductENSG00000108691 (Ensembl)
CCL2ProteinP13500 (Uniprot-TrEMBL)
DCP2 ProteinQ8IU60 (Uniprot-TrEMBL)
DDIT3 geneGeneProductENSG00000175197 (Ensembl)
DDIT3ProteinP35638 (Uniprot-TrEMBL)
DIS3 ProteinQ9Y2L1 (Uniprot-TrEMBL)
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)
HERPUD1 geneGeneProductENSG00000051108 (Ensembl)
HERPUD1ProteinQ15011 (Uniprot-TrEMBL)
IGFBP1ProteinP08833 (Uniprot-TrEMBL)
IGFPB1 geneGeneProductENSG00000146678 (Ensembl)
IL8 geneGeneProductENSG00000169429 (Ensembl)
IL8ProteinP10145 (Uniprot-TrEMBL)
KSRP ProteinQ92945 (Uniprot-TrEMBL)
KSRP:mRNA Degradation ComplexComplexR-HSA-450479 (Reactome)
NF-YComplexR-HSA-381204 (Reactome) NF-Y is a ubiquitous heterotrimeric transcription factor comprising subunits NF-Y A, NF-Y B, and NF-Y C. It binds the sequence CCAAT.
NFYA ProteinP23511 (Uniprot-TrEMBL)
NFYB ProteinP25208 (Uniprot-TrEMBL)
NFYC ProteinQ13952 (Uniprot-TrEMBL)
PARN ProteinO95453 (Uniprot-TrEMBL)
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.

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ASNS geneR-HSA-1791118 (Reactome)
ASNSArrowR-HSA-1791118 (Reactome)
ATF3 geneR-HSA-1791173 (Reactome)
ATF3ArrowR-HSA-1791173 (Reactome)
ATF4ArrowR-HSA-1791056 (Reactome)
ATF4ArrowR-HSA-1791095 (Reactome)
ATF4ArrowR-HSA-1791107 (Reactome)
ATF4ArrowR-HSA-1791118 (Reactome)
ATF4ArrowR-HSA-1791173 (Reactome)
ATF4ArrowR-HSA-1791180 (Reactome)
ATF4ArrowR-HSA-517731 (Reactome)
ATF6(1-380)ArrowR-HSA-1791107 (Reactome)
CCL2 geneR-HSA-1791056 (Reactome)
CCL2ArrowR-HSA-1791056 (Reactome)
DDIT3 geneR-HSA-1791107 (Reactome)
DDIT3ArrowR-HSA-1791107 (Reactome)
HERPUD1 geneR-HSA-1791095 (Reactome)
HERPUD1ArrowR-HSA-1791095 (Reactome)
IGFBP1ArrowR-HSA-1791180 (Reactome)
IGFPB1 geneR-HSA-1791180 (Reactome)
IL8 geneR-HSA-517731 (Reactome)
IL8ArrowR-HSA-517731 (Reactome)
KSRP:mRNA Degradation ComplexTBarR-HSA-517731 (Reactome)
NF-YArrowR-HSA-1791107 (Reactome)
R-HSA-1791056 (Reactome) The CCL2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1791095 (Reactome) The HERPUD gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1791107 (Reactome) The CHOP (DDIT3) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1791118 (Reactome) The Aspariagine Synthetase (ASNS) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1791173 (Reactome) The ATF3 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1791180 (Reactome) The IGFBP1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-517731 (Reactome) The IL-8 gene is transcribed to yield mRNA which is translated to yield protein.
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