ATF4 activates genes in response to endoplasmic reticulum stress (Homo sapiens)

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Bibliography

1. Balasubramanian MN, Shan J, Kilberg MS.; ''Dynamic changes in genomic histone association and modification during activation of the ASNS and ATF3 genes by amino acid limitation.''; PubMed Europe PMC Scholia
2. Hayner JN, Shan J, Kilberg MS.; ''Regulation of the ATF3 gene by a single promoter in response to amino acid availability and endoplasmic reticulum stress in human primary hepatocytes and hepatoma cells.''; PubMed Europe PMC Scholia
3. 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 Scholia
4. Chen H, Pan YX, Dudenhausen EE, Kilberg MS.; ''Amino acid deprivation induces the transcription rate of the human asparagine synthetase gene through a timed program of expression and promoter binding of nutrient-responsive basic region/leucine zipper transcription factors as well as localized histone acetylation.''; PubMed Europe PMC Scholia
5. Mukaida N, Shiroo M, Matsushima K.; ''Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8.''; PubMed Europe PMC Scholia
6. Sikalidis AK, Lee JI, Stipanuk MH.; ''Gene expression and integrated stress response in HepG2/C3A cells cultured in amino acid deficient medium.''; PubMed Europe PMC Scholia
7. Yamaguchi Y, Larkin D, Lara-Lemus R, Ramos-Castañeda 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 Scholia
8. Kowalski J, Denhardt DT.; ''Regulation of the mRNA for monocyte-derived neutrophil-activating peptide in differentiating HL60 promyelocytes.''; PubMed Europe PMC Scholia
9. 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 Scholia
10. 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 Scholia
11. 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 Scholia
12. 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 Scholia
13. Pan YX, Chen H, Thiaville MM, Kilberg MS.; ''Activation of the ATF3 gene through a co-ordinated amino acid-sensing response programme that controls transcriptional regulation of responsive genes following amino acid limitation.''; PubMed Europe PMC Scholia
14. 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
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 Scholia
16. 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 Scholia
17. 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 Scholia
18. 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 Scholia
19. 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 Scholia
20. 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
21. 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
22. Lee SH, Min KW, Zhang X, Baek SJ.; ''3,3'-diindolylmethane induces activating transcription factor 3 (ATF3) via ATF4 in human colorectal cancer cells.''; PubMed Europe PMC Scholia
23. Takayanagi S, Fukuda R, Takeuchi Y, Tsukada S, Yoshida K.; ''Gene regulatory network of unfolded protein response genes in endoplasmic reticulum stress.''; PubMed Europe PMC Scholia
24. Lee JI, Dominy JE, Sikalidis AK, Hirschberger LL, Wang W, Stipanuk MH.; ''HepG2/C3A cells respond to cysteine deprivation by induction of the amino acid deprivation/integrated stress response pathway.''; PubMed Europe PMC Scholia
25. 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
26. Fu L, Kilberg MS.; ''Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
ASNS gene	Protein	ENSG00000070669 (Ensembl)
ASNS gene	GeneProduct	ENSG00000070669 (Ensembl)
ASNS	Protein	P08243 (Uniprot-TrEMBL)
ATF3 gene	Protein	ENSG00000162772 (Ensembl)
ATF3 gene	GeneProduct	ENSG00000162772 (Ensembl)
ATF3	Protein	P18847 (Uniprot-TrEMBL)
ATF4	Protein	P18848 (Uniprot-TrEMBL)
ATF4:ATF3 gene	Complex	R-HSA-9635905 (Reactome)
ATF4:CEBPB,CEBPG:ASNS gene	Complex	R-HSA-9635898 (Reactome)
ATF4	Protein	P18848 (Uniprot-TrEMBL)
ATF6(1-380)	Protein	P18850 (Uniprot-TrEMBL)
CCL2 gene	GeneProduct	ENSG00000108691 (Ensembl)
CCL2	Protein	P13500 (Uniprot-TrEMBL)
CEBPB	Protein	P17676 (Uniprot-TrEMBL)
CEBPG	Protein	P53567 (Uniprot-TrEMBL)
DCP2	Protein	Q8IU60 (Uniprot-TrEMBL)
DDIT3 gene	GeneProduct	ENSG00000175197 (Ensembl)
DDIT3	Protein	P35638 (Uniprot-TrEMBL)
DIS3	Protein	Q9Y2L1 (Uniprot-TrEMBL)
EXOSC1	Protein	Q9Y3B2 (Uniprot-TrEMBL)
EXOSC2	Protein	Q13868 (Uniprot-TrEMBL)
EXOSC3	Protein	Q9NQT5 (Uniprot-TrEMBL)
EXOSC4	Protein	Q9NPD3 (Uniprot-TrEMBL)
EXOSC5	Protein	Q9NQT4 (Uniprot-TrEMBL)
EXOSC6	Protein	Q5RKV6 (Uniprot-TrEMBL)
EXOSC7	Protein	Q15024 (Uniprot-TrEMBL)
EXOSC8	Protein	Q96B26 (Uniprot-TrEMBL)
EXOSC9	Protein	Q06265 (Uniprot-TrEMBL)
HERPUD1 gene	GeneProduct	ENSG00000051108 (Ensembl)
HERPUD1	Protein	Q15011 (Uniprot-TrEMBL)
IGFBP1	Protein	P08833 (Uniprot-TrEMBL)
IGFPB1 gene	GeneProduct	ENSG00000146678 (Ensembl)
IL8 gene	GeneProduct	ENSG00000169429 (Ensembl)
IL8	Protein	P10145 (Uniprot-TrEMBL)
KSRP	Protein	Q92945 (Uniprot-TrEMBL)
KSRP:mRNA Degradation Complex	Complex	R-HSA-450479 (Reactome)
NF-Y	Complex	R-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	Protein	P23511 (Uniprot-TrEMBL)
NFYB	Protein	P25208 (Uniprot-TrEMBL)
NFYC	Protein	Q13952 (Uniprot-TrEMBL)
PARN	Protein	O95453 (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

Source	Target	Type	Database reference	Comment
ASNS gene			R-HSA-1791118 (Reactome)
	ASNS	Arrow	R-HSA-1791118 (Reactome)
ATF3 gene			R-HSA-1791173 (Reactome)
	ATF3	Arrow	R-HSA-1791173 (Reactome)
ATF4:ATF3 gene		Arrow	R-HSA-1791173 (Reactome)
ATF4:CEBPB,CEBPG:ASNS gene		Arrow	R-HSA-1791118 (Reactome)
ATF4		Arrow	R-HSA-1791056 (Reactome)
ATF4		Arrow	R-HSA-1791095 (Reactome)
ATF4		Arrow	R-HSA-1791107 (Reactome)
ATF4		Arrow	R-HSA-1791180 (Reactome)
ATF4		Arrow	R-HSA-517731 (Reactome)
ATF6(1-380)		Arrow	R-HSA-1791107 (Reactome)
CCL2 gene			R-HSA-1791056 (Reactome)
	CCL2	Arrow	R-HSA-1791056 (Reactome)
DDIT3 gene			R-HSA-1791107 (Reactome)
	DDIT3	Arrow	R-HSA-1791107 (Reactome)
HERPUD1 gene			R-HSA-1791095 (Reactome)
	HERPUD1	Arrow	R-HSA-1791095 (Reactome)
	IGFBP1	Arrow	R-HSA-1791180 (Reactome)
IGFPB1 gene			R-HSA-1791180 (Reactome)
IL8 gene			R-HSA-517731 (Reactome)
	IL8	Arrow	R-HSA-517731 (Reactome)
KSRP:mRNA Degradation Complex		TBar	R-HSA-517731 (Reactome)
NF-Y		Arrow	R-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 DDIT3 (CHOP) gene is transcribed to yield mRNA and the mRNA is translated to yield protein (Bartlett et al. 1992, Carlson et al. 1993, Bruhat et al. 1997, Yoshida et al. 2000, Lee et al. 2008, Sikalidis et al. 2011). In response to amino acid starvation, transcription of DDIT3 s enhanced by ATF4 and phosphorylated ATF2 (Bruhat et al. 2000, Averous et al. 2004, Bruhat et al. 2007)
			R-HSA-1791118 (Reactome)	The Asparagine Synthetase (ASNS) gene is transcribed to yield mRNA and the mRNA is translated to yield protein (Chen et al. 2004, Lee et al. 2008, Gjymishka et al. 2009, Sikalidis et al. 2011, Balasubramanian et al. 2013, inferred from the mouse homolog). Transcription of ASNS is activated by the unfolded protein response (Gjymishka et al. 2009), amino acid deficiency (Chen et al. 2004, Lee et al. 2008, Sikalidis et al. 2011, Balasubramanian et al. 2013, inferred from the mouse homolog), and heme deficiency (inferred from the mouse homolog).
			R-HSA-1791173 (Reactome)	The ATF3 gene is transcribed to yield mRNA and the mRNA is translated to yield protein (Chen et al. 2004, Pan et al. 2007, Lee et al. 2008, Armstrong et al. 2010, Sikalidis et al. 2011, Fu and Kilberg 2013, Lee et al. 2013, Hayner et al. 2018). Transcription of ATF3 is enhanced in response to amino acid deficiency (Chen et al. 2004, Pan et al. 2007, Lee et al. 2008, Sikaldis et al. 2011, Fu and Kilberg 2013, Hayner et al. 2018). ATF4 binds a CEBP-ATF response element (CARE) and an additional upstream element in the promoter of the ATF3 gene, resulting in enhanced transcription (Pan et al. 2007, Armstrong et al. 2010, Fu and Kilberg 2013, Lee et al. 2013, Hayner et al. 2018, and inferred from mouse homologs). CEBPB and ATF3 bind later and correlate with reduced expression of ATF4 (Pan et al. 2007)
			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.