Gene Symbol: ATF4
Description: activating transcription factor 4
Alias: CREB-2, CREB2, TAXREB67, TXREB, cyclic AMP-dependent transcription factor ATF-4, DNA-binding protein TAXREB67, cAMP response element-binding protein 2, cAMP-dependent transcription factor ATF-4, cAMP-responsive element-binding protein 2, cyclic AMP-responsive element-binding protein 2, tax-responsive enhancer element B67, tax-responsive enhancer element-binding protein 67
Species: human
Products:     ATF4

Top Publications

  1. Su N, Kilberg M. C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene. J Biol Chem. 2008;283:35106-17 pubmed publisher
    ..ASNS) gene and inhibited transcription from a reporter gene driven by the ASNS promoter following activation by ATF4 or amino acid deprivation...
  2. Wang Q, Mora Jensen H, Weniger M, Perez Galan P, Wolford C, Hai T, et al. ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells. Proc Natl Acad Sci U S A. 2009;106:2200-5 pubmed publisher
    ..elicit an integrated stress response program at the ER to activate the CREB/ATF transcription factors ATF3 and ATF4. We show that ATF3 and ATF4 form a complex capable of binding to the NOXA promoter, which is required for NOXA ..
  3. Rutkowski D, Kaufman R. All roads lead to ATF4. Dev Cell. 2003;4:442-4 pubmed
    ..of the translation initiation factor eIF2alpha and subsequent translational activation of the transcription factor ATF4. Exploring the consequences of this event has highlighted the ways in which stress is sensed and responded to via ..
  4. Ohoka N, Yoshii S, Hattori T, Onozaki K, Hayashi H. TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J. 2005;24:1243-55 pubmed
    ..region in the TRB3 promoter contains amino-acid response elements overlapping the CHOP-binding site, and CHOP and ATF4 cooperated to activate this promoter activity...
  5. Marchand A, Tomkiewicz C, Magne L, Barouki R, Garlatti M. Endoplasmic reticulum stress induction of insulin-like growth factor-binding protein-1 involves ATF4. J Biol Chem. 2006;281:19124-33 pubmed
    ..A distal regulatory region of the human IGFBP-1 gene (-6682/-6384) containing an activating transcription factor 4 (ATF4) composite site was required for promoter activation upon ER stress...
  6. Roybal C, Yang S, Sun C, Hurtado D, Vander Jagt D, Townes T, et al. Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J Biol Chem. 2004;279:14844-52 pubmed
    ..Homocysteine treatment caused transient phosphorylation of eIF2alpha and an increase in ATF4 protein level...
  7. 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. J Biol Chem. 2004;279:5288-97 pubmed
    ..Among all these transcription factors, only ATF4 and ATF2 are involved in the amino acid control of CHOP expression...
  8. Korfei M, Ruppert C, Mahavadi P, Henneke I, Markart P, Koch M, et al. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008;178:838-46 pubmed publisher
    ..Severe ER stress response in the AECIIs of patients with sporadic IPF may underlie the apoptosis of this cell type and development of fibrosis in this disease. ..
  9. Shan J, Ord D, Ord T, Kilberg M. Elevated ATF4 expression, in the absence of other signals, is sufficient for transcriptional induction via CCAAT enhancer-binding protein-activating transcription factor response elements. J Biol Chem. 2009;284:21241-8 pubmed publisher
    ..In a self-limiting transcriptional program, ATF4 transiently activates a wide range of downstream target genes involved in transport, cellular metabolism, and other ..

More Information


  1. Karpinski B, Morle G, Huggenvik J, Uhler M, Leiden J. Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element. Proc Natl Acad Sci U S A. 1992;89:4820-4 pubmed
    ..These results demonstrate that CRE-dependent transcription can be both positively and negatively regulated by structurally related members of the ATF/CREB family. ..
  2. He C, Gong P, Hu B, Stewart D, Choi M, Choi A, et al. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J Biol Chem. 2001;276:20858-65 pubmed
    ..Association between Nrf2 and ATF4 in mammalian cells was confirmed by co-immunoprecipitation and mammalian two-hybrid assays. Furthermore, Nrf2...
  3. White J, McIllhinney R, Wise A, Ciruela F, Chan W, Emson P, et al. The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx. Proc Natl Acad Sci U S A. 2000;97:13967-72 pubmed
    ..interactions between the C-terminal tails of GABA(B)-R1 and GABA(B)-R2 with two related transcription factors, CREB2 (ATF4) and ATFx...
  4. Rzymski T, Milani M, Pike L, Buffa F, Mellor H, Winchester L, et al. Regulation of autophagy by ATF4 in response to severe hypoxia. Oncogene. 2010;29:4424-35 pubmed publisher
    Activating transcription factor 4 (ATF4) is a transcription factor induced under severe hypoxia and a component of the PERK pathway involved in the unfolded protein response (UPR), a process that protects cells from the negative ..
  5. Kawai T, Matsumoto M, Takeda K, Sanjo H, Akira S. ZIP kinase, a novel serine/threonine kinase which mediates apoptosis. Mol Cell Biol. 1998;18:1642-51 pubmed
    ..ZIP kinase physically binds to ATF4, a member of the activating transcription factor/cyclic AMP-responsive element-binding protein (ATF/CREB) family, ..
  6. Oh Y, Liu X, Yue P, Kang S, Chen J, Taunton J, et al. ERK/ribosomal S6 kinase (RSK) signaling positively regulates death receptor 5 expression through co-activation of CHOP and Elk1. J Biol Chem. 2010;285:41310-9 pubmed publisher
    ..Additionally, celecoxib increased CHOP promoter activity in an ATF4-dependent manner, and siRNA-mediated blockade of ATF4 abrogated both CHOP induction and DR5 up-regulation, ..
  7. Dey S, Baird T, Zhou D, Palam L, Spandau D, Wek R. Both transcriptional regulation and translational control of ATF4 are central to the integrated stress response. J Biol Chem. 2010;285:33165-74 pubmed publisher
    ..stresses, phosphorylation of eIF2 (eIF2?P) represses global translation coincident with preferential translation of ATF4. ATF4 is a transcriptional activator of the integrated stress response, a program of gene expression involved in ..
  8. Ye J, Kumanova M, Hart L, Sloane K, Zhang H, De Panis D, et al. The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. EMBO J. 2010;29:2082-96 pubmed publisher
    The transcription factor ATF4 regulates the expression of genes involved in amino acid metabolism, redox homeostasis and ER stress responses, and it is overexpressed in human solid tumours, suggesting that it has an important function in ..
  9. Zhu H, Xia L, Zhang Y, Wang H, Xu W, Hu H, et al. Activating transcription factor 4 confers a multidrug resistance phenotype to gastric cancer cells through transactivation of SIRT1 expression. PLoS ONE. 2012;7:e31431 pubmed publisher
    ..Activating transcription factor 4 (ATF4) is a stress response gene involved in homeostasis and cellular protection...
  10. Oskolkova O, Afonyushkin T, Leitner A, von Schlieffen E, Gargalovic P, Lusis A, et al. ATF4-dependent transcription is a key mechanism in VEGF up-regulation by oxidized phospholipids: critical role of oxidized sn-2 residues in activation of unfolded protein response. Blood. 2008;112:330-9 pubmed publisher
    ..OxPLs induced protein expression of activating transcription factor-4 (ATF4), an important effector of UPR...
  11. Pons J, Evrard Todeschi N, Bertho G, Gharbi Benarous J, Benarous R, Girault J. Phosphorylation-dependent structure of ATF4 peptides derived from a human ATF4 protein, a member of the family of transcription factors. Peptides. 2007;28:2253-67 pubmed
    b>ATF4 plays a crucial role in the cellular response to stress and the F-box protein beta-TrCP, the receptor component of the SCF E3 ubiquitin ligase responsible for ATF4 degradation by the proteasome, binds to ATF4, and controls its ..
  12. Fung H, Liu P, Demple B. ATF4-dependent oxidative induction of the DNA repair enzyme Ape1 counteracts arsenite cytotoxicity and suppresses arsenite-mediated mutagenesis. Mol Cell Biol. 2007;27:8834-47 pubmed
    ..Electrophoretic mobility shift assays indicated that an ATF4/c-Jun heterodimer was the responsible transcription factor...
  13. Shimizu M, Li J, Maruyama R, Inoue J, Sato R. FGF19 (fibroblast growth factor 19) as a novel target gene for activating transcription factor 4 in response to endoplasmic reticulum stress. Biochem J. 2013;450:221-9 pubmed publisher
    ..element) was localized in this region, and this site was responsible for inducing its transcription through ATF4 (activating transcription factor 4), which is activated in response to ER stress...
  14. De Angelis R, Iezzi S, Bruno T, Corbi N, Di Padova M, Floridi A, et al. Functional interaction of the subunit 3 of RNA polymerase II (RPB3) with transcription factor-4 (ATF4). FEBS Lett. 2003;547:15-9 pubmed
    ..In this paper we report the interaction between RPB3 and another known transcription factor, ATF4. We found that the intensity of the interaction between RPB3 and ATF4 is similar to the one between RPB3 and ..
  15. Hai T, Curran T. Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci U S A. 1991;88:3720-4 pubmed
    ..These findings indicate that the Fos/Jun and ATF/CREB families of transcription factors are not as distinct as was previously thought. We suggest that they can be grouped into a superfamily of transcription factors. ..
  16. Liang G, Hai T. Characterization of human activating transcription factor 4, a transcriptional activator that interacts with multiple domains of cAMP-responsive element-binding protein (CREB)-binding protein. J Biol Chem. 1997;272:24088-95 pubmed
    ..Consistent with its role as a coactivator, CBP potentiates the ability of hATF4 to activate transcription. The potential significance of the interaction between hATF4 and multiple factors is discussed. ..
  17. Gachon F, Gaudray G, Thebault S, Basbous J, Koffi J, Devaux C, et al. The cAMP response element binding protein-2 (CREB-2) can interact with the C/EBP-homologous protein (CHOP). FEBS Lett. 2001;502:57-62 pubmed
    ..Cotransfection of CHOP with CREB-2 results in decreased activation driven by the cellular CRE motif or the HTLV-I proximal Tax-responsive element, confirming that CREB-2 and CHOP can interact with each other in vivo. ..
  18. Siu F, Bain P, LeBlanc Chaffin R, Chen H, Kilberg M. ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene. J Biol Chem. 2002;277:24120-7 pubmed
    ..The results indicated that ATF4 binds to the NSRE-1 sequence and that the amount of the ATF4 complex was increased when extracts from amino acid-..
  19. Morris J, Kandpal G, Ma L, Austin C. DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. Hum Mol Genet. 2003;12:1591-608 pubmed
    ..alpha-actinin2 and beta4-spectrin; and proteins which transduce signals from membrane receptors, including ATF4 and ATF5. Truncated mutant DISC1 fails to interact with ATF4, ATF5 or NUDEL...
  20. Jiang Q, Li F, Shi K, Wu P, An J, Yang Y, et al. ATF4 activation by the p38MAPK-eIF4E axis mediates apoptosis and autophagy induced by selenite in Jurkat cells. FEBS Lett. 2013;587:2420-9 pubmed publisher
    ..for the phosphorylation of eIF4E, thus initiating the translation of ER stress-related transcription factor ATF4. Upregulated ATF4 results in the transcriptional initiation of the apoptosis-related chop gene and autophagy-..
  21. Oyadomari S, Mori M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 2004;11:381-9 pubmed
    ..Here, we summarize the current understanding of the roles of CHOP/GADD153 in ER stress-mediated apoptosis and in diseases including diabetes, brain ischemia and neurodegenerative disease. ..
  22. Tanabe M, Izumi H, Ise T, Higuchi S, Yamori T, Yasumoto K, et al. Activating transcription factor 4 increases the cisplatin resistance of human cancer cell lines. Cancer Res. 2003;63:8592-5 pubmed
    ..One of the cisplatin-inducible genes was identified as activating transcription factor 4 (ATF4). Northern blot analysis demonstrated that expression of ATF4 is inducible at the transcriptional level...
  23. Zhou D, Palam L, Jiang L, Narasimhan J, Staschke K, Wek R. Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditions. J Biol Chem. 2008;283:7064-73 pubmed publisher
    ..Central to the eIF2 kinase response is the preferential translation of ATF4 mRNA, encoding a transcriptional activator of genes involved in stress remediation...
  24. Millar J, Christie S, Porteous D. Yeast two-hybrid screens implicate DISC1 in brain development and function. Biochem Biophys Res Commun. 2003;311:1019-25 pubmed
    ..Intriguingly, mutations in one of the proteins identified, WKL1, have been previously suggested to underlie the aetiology of catatonic schizophrenia. ..
  25. Vattem K, Wek R. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proc Natl Acad Sci U S A. 2004;101:11269-74 pubmed
    ..Central to this stress response is the transcriptional regulator activating transcription factor, ATF4. Here we describe the mechanism regulating ATF4 expression involving the differential contribution of two upstream ..
  26. Milani M, Rzymski T, Mellor H, Pike L, Bottini A, Generali D, et al. The role of ATF4 stabilization and autophagy in resistance of breast cancer cells treated with Bortezomib. Cancer Res. 2009;69:4415-23 pubmed publisher
    ..We show that induction of autophagy by Bortezomib is dependent on the proteasomal stabilisation of ATF4 and up-regulation of LC3B by ATF4...
  27. Ord D, Meerits K, Ord T. TRB3 protects cells against the growth inhibitory and cytotoxic effect of ATF4. Exp Cell Res. 2007;313:3556-67 pubmed
    ..We and other researchers have previously shown that TRB3 interacts with activating transcription factor 4 (ATF4) and may function as a negative feedback regulator of ATF4...
  28. Carraro V, Maurin A, Lambert Langlais S, Averous J, Chaveroux C, Parry L, et al. Amino acid availability controls TRB3 transcription in liver through the GCN2/eIF2?/ATF4 pathway. PLoS ONE. 2010;5:e15716 pubmed publisher
    ..the characterization of a functional Amino Acid Response Element (AARE) in the TRB3 promoter and the binding of ATF4, ATF2 and C/EBP? to this AARE sequence...
  29. Jousse C, Deval C, Maurin A, Parry L, Cherasse Y, Chaveroux C, et al. TRB3 inhibits the transcriptional activation of stress-regulated genes by a negative feedback on the ATF4 pathway. J Biol Chem. 2007;282:15851-61 pubmed
    ..conserved response to several stresses that converge to the induction of the activating transcription factor 4 (ATF4)...
  30. Afonyushkin T, Oskolkova O, Philippova M, Resink T, Erne P, Binder B, et al. Oxidized phospholipids regulate expression of ATF4 and VEGF in endothelial cells via NRF2-dependent mechanism: novel point of convergence between electrophilic and unfolded protein stress pathways. Arterioscler Thromb Vasc Biol. 2010;30:1007-13 pubmed publisher
    The ATF4 arm of the unfolded protein response is increasingly recognized for its relevance to pathology, and in particular to angiogenic reactions...
  31. Lassot I, Segeral E, Berlioz Torrent C, Durand H, Groussin L, Hai T, et al. ATF4 degradation relies on a phosphorylation-dependent interaction with the SCF(betaTrCP) ubiquitin ligase. Mol Cell Biol. 2001;21:2192-202 pubmed
    ..E3 ubiquitin ligase responsible for IkappaBalpha and beta-catenin degradation, is colocalized in the nucleus with ATF4, a member of the ATF-CREB bZIP family of transcription factors, and controls its stability...
  32. Outinen P, Sood S, Pfeifer S, Pamidi S, Podor T, Li J, et al. Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells. Blood. 1999;94:959-67 pubmed
  33. Chen H, Pan Y, Dudenhausen E, Kilberg M. 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 his. J Biol Chem. 2004;279:50829-39 pubmed
    ..overexpression and electrophoresis mobility shift analysis showed the involvement of the transcription factors ATF4, C/EBPbeta, and ATF3-FL through the nutrient-sensing response element-1 (NSRE-1) within the ASNS promoter...
  34. Martínez Reyes I, Sánchez Aragó M, Cuezva J. AMPK and GCN2-ATF4 signal the repression of mitochondria in colon cancer cells. Biochem J. 2012;444:249-59 pubmed publisher
    ..Changes in the bioenergetic function of mitochondria are mimicked by the activation of AMPK and the silencing of ATF4 (activating transcription factor 4)...
  35. Armstrong J, Flockhart R, Veal G, Lovat P, Redfern C. Regulation of endoplasmic reticulum stress-induced cell death by ATF4 in neuroectodermal tumor cells. J Biol Chem. 2010;285:6091-100 pubmed publisher
    ..pathways induced by fenretinide and bortezomib are mediated by the eukaryotic initiation factor 2alpha (eIF2alpha)-ATF4 signaling pathway...
  36. Lassot I, Estrabaud E, Emiliani S, Benkirane M, Benarous R, Margottin Goguet F. p300 modulates ATF4 stability and transcriptional activity independently of its acetyltransferase domain. J Biol Chem. 2005;280:41537-45 pubmed
    b>ATF4 plays a crucial role in the cellular response to stress and multiple stress responses pathways converge to the translational up-regulation of ATF4...
  37. Roybal C, Hunsaker L, Barbash O, Vander Jagt D, Abcouwer S. The oxidative stressor arsenite activates vascular endothelial growth factor mRNA transcription by an ATF4-dependent mechanism. J Biol Chem. 2005;280:20331-9 pubmed
    ..reticulum stressor, increases VEGF transcription by a mechanism dependent upon activating transcription factor ATF4. Because ATF4 is expressed in response to oxidative stress, we hypothesized that ATF4 was also responsible for ..
  38. Luo S, Baumeister P, Yang S, Abcouwer S, Lee A. Induction of Grp78/BiP by translational block: activation of the Grp78 promoter by ATF4 through and upstream ATF/CRE site independent of the endoplasmic reticulum stress elements. J Biol Chem. 2003;278:37375-85 pubmed
    ..We report here that ATF4, a transcription factor whose translation is up-regulated by the PERK-eIF2alpha pathway, can activate the Grp78 ..
  39. Frank C, Ge X, Xie Z, Zhou Y, Tsai L. Control of activating transcription factor 4 (ATF4) persistence by multisite phosphorylation impacts cell cycle progression and neurogenesis. J Biol Chem. 2010;285:33324-37 pubmed publisher
    ..In this study, we describe a novel mechanism controlling the persistence of the transcription factor ATF4 by multisite phosphorylation...
  40. Yonekura S, Tsuchiya M, Tokutake Y, Mizusawa M, Nakano M, Miyaji M, et al. The unfolded protein response is involved in both differentiation and apoptosis of bovine mammary epithelial cells. J Dairy Sci. 2018;101:3568-3578 pubmed publisher
    ..Expression levels of the spliced X-box binding protein 1 (XBP1) and activating transcription factor 4 (ATF4) were found to be significantly higher in the mammary gland tissue 10 d before delivery compared with 40 d before ..
  41. Srivastava R, Li C, Ahmad A, Abrams O, Gorbatyuk M, Harrod K, et al. ATF4 regulates arsenic trioxide-mediated NADPH oxidase, ER-mitochondrial crosstalk and apoptosis. Arch Biochem Biophys. 2016;609:39-50 pubmed publisher
    ..Here, we show that arsenic induction of the UPR triggers ATF4, which is involved in regulating this ER-mitochondrial crosstalk that is important for the molecular pathogenesis ..
  42. Cui X, Tan J, Shi Y, Sun C, Li Y, Ji C, et al. The long non-coding RNA Gm10768 activates hepatic gluconeogenesis by sequestering microRNA-214 in mice. J Biol Chem. 2018;293:4097-4109 pubmed publisher
    ..Gm10768 sequestrated microRNA-214 (miR-214) to relieve its suppression on activating transcription factor 4 (ATF4), a positive regulator of hepatic gluconeogenesis...
  43. Salminen A, Kaarniranta K, Kauppinen A. Integrated stress response stimulates FGF21 expression: Systemic enhancer of longevity. Cell Signal. 2017;40:10-21 pubmed publisher
    ..kinases of the integrated stress response (ISR) pathway stimulate the expression of FGF21 through the activation of ATF4 transcription factor, thus enhancing cellular stress resistance...
  44. Liu D, Zhang Y, Li X, Li J, Yang S, Xing X, et al. eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress. Sci Rep. 2017;7:5062 pubmed publisher
    ..Salubrinal also protected osteoblast development by upregulating the levels of ATF4, ALP and RUNX2, and it stimulated angiogenesis of endothelial cells through elevating ATF4 and VEGF...
  45. Chen D, Fan Z, Rauh M, Buchfelder M, Eyupoglu I, Savaskan N. ATF4 promotes angiogenesis and neuronal cell death and confers ferroptosis in a xCT-dependent manner. Oncogene. 2017;36:5593-5608 pubmed publisher
    Activating transcription factor 4 (ATF4) is a critical mediator of metabolic and oxidative homeostasis and cell survival...
  46. Bao Q, Zhao M, Chen L, Wang Y, Wu S, Wu W, et al. MicroRNA-297 promotes cardiomyocyte hypertrophy via targeting sigma-1 receptor. Life Sci. 2017;175:1-10 pubmed publisher
    ..of miR-297 inhibited the activation of X-box binding protein 1 (Xbp1) and activating transcriptional factor 4 (ATF4) signaling pathways in NCMs...
  47. Basu M, Courtney S, Brinton M. Arsenite-induced stress granule formation is inhibited by elevated levels of reduced glutathione in West Nile virus-infected cells. PLoS Pathog. 2017;13:e1006240 pubmed publisher
    ..The transcription factors, Nrf2 and ATF4, which activate antioxidant genes, were upregulated and translocated to the nucleus...
  48. Liu F, Weng X, Lin P, Zheng C, Xu H, Liu X, et al. Duhuo Jisheng decoction inhibits endoplasmic reticulum stress in chondrocytes induced by tunicamycin through the downregulation of miR-34a. Int J Mol Med. 2015;36:1311-8 pubmed publisher
    ..showed that the expression levels of Xbp1, Xbp1s and Bcl‑2 were increased, and the expression levels of Bip, Atf4, Chop, Bax, caspase‑9 and ‑3 were decreased in the TM‑exposed chondrocytes treated with DHJSD ..
  49. Gjymishka A, Palii S, Shan J, Kilberg M. Despite increased ATF4 binding at the C/EBP-ATF composite site following activation of the unfolded protein response, system A transporter 2 (SNAT2) transcription activity is repressed in HepG2 cells. J Biol Chem. 2008;283:27736-47 pubmed publisher
    ..protein synthesis but enhances translation of selected mRNAs such as that for activating transcription factor 4 (ATF4)...
  50. Malavasi E, Ogawa F, Porteous D, Millar J. DISC1 variants 37W and 607F disrupt its nuclear targeting and regulatory role in ATF4-mediated transcription. Hum Mol Genet. 2012;21:2779-92 pubmed publisher
    ..In the nucleus, DISC1 interacts with the transcription factor Activating Transcription Factor 4 (ATF4), which is involved in the regulation of cellular stress responses, emotional behaviour and memory consolidation...
  51. Liew C, Bochenski J, Kawamori D, Hu J, Leech C, Wanic K, et al. The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta cells. J Clin Invest. 2010;120:2876-88 pubmed publisher
    ..Further analysis in MIN6 cells demonstrated that TRB3 interacted with the transcription factor ATF4 and that this complex acted as a competitive inhibitor of cAMP response element-binding (CREB) transcription factor ..
  52. Jin H, Seo S, Woo S, Choe T, Hong S, Kim J, et al. Nuclear protein 1 induced by ATF4 in response to various stressors acts as a positive regulator on the transcriptional activation of ATF4. IUBMB Life. 2009;61:1153-8 pubmed publisher
    ..this study, we found that the expression of NUPR1 by various stresses induced by activating transcription factor 4 (ATF4). Loss of ATF4 using siRNA significantly diminished NUPR1 expression...
  53. Palam L, Gore J, Craven K, Wilson J, Korc M. Integrated stress response is critical for gemcitabine resistance in pancreatic ductal adenocarcinoma. Cell Death Dis. 2015;6:e1913 pubmed publisher
    ..Gem induced eIF2 phosphorylation and downstream transcription factors ATF4 and CHOP in PCCs, and these effects occurred in an eIF2α-S51 phosphorylation-dependent manner as determined ..
  54. Chen X, Zhang X, Chen J, Yang Q, Yang L, Xu D, et al. Hinokitiol copper complex inhibits proteasomal deubiquitination and induces paraptosis-like cell death in human cancer cells. Eur J Pharmacol. 2017;815:147-155 pubmed publisher
    ..and paraptosis-like cell death in A549 and K562 cells, and (4) HK-Cu-induced cell death depends on ATF4-assosiated ER stress but is apparently not related to ROS generation...
  55. Li R, Zhou P, Guo Y, Lee J, Zhou B. Tris (1,3-dichloro-2-propyl) phosphate-induced apoptotic signaling pathways in SH-SY5Y neuroblastoma cells. Neurotoxicology. 2017;58:1-10 pubmed publisher
    ..stress, including eukaryotic translation initiation factor 2a subunit (p-EIF2a), activation transcription factor (ATF4), glucose-regulated protein (GRP78), and the proapoptotic factor C/EBP homologous protein (CHOP)...
  56. Wengrod J, Martin L, Wang D, Frischmeyer Guerrerio P, Dietz H, Gardner L. Inhibition of nonsense-mediated RNA decay activates autophagy. Mol Cell Biol. 2013;33:2128-35 pubmed publisher
    ..The regulation of autophagy by NMD is due, in part, to stabilization of the documented NMD target ATF4. NMD inhibition increases intracellular amino acids, a hallmark of autophagy, and the concomitant inhibition of ..
  57. Sun X, Liu J, Crary J, Malagelada C, Sulzer D, Greene L, et al. ATF4 protects against neuronal death in cellular Parkinson's disease models by maintaining levels of parkin. J Neurosci. 2013;33:2398-407 pubmed publisher
    ..The transcription factor ATF4 (activating transcription factor 4) is induced by multiple PD-relevant stressors, such as endoplasmic reticulum ..
  58. Ferguson J, Smith M, Zudaire I, Wellbrock C, Arozarena I. Glucose availability controls ATF4-mediated MITF suppression to drive melanoma cell growth. Oncotarget. 2017;8:32946-32959 pubmed publisher
    ..Our data give new insight into the complex regulation of MITF, a key regulator of melanoma biology, and support previous findings that link metabolic disorders such as hyperglycemia and diabetes with increased melanoma risk. ..
  59. Xia H, Zhu J, Wang J, Ren J, Cai Y, Wang F, et al. Association of ATF4 Expression With Tissue Hypoxia and M2 Macrophage Infiltration in Infantile Hemangioma. J Histochem Cytochem. 2017;65:285-294 pubmed publisher
    ..Activating transcription factor 4 (ATF4), an important gene mediating cellular adaptation to various stress signals, could confer a survival advantage for ..
  60. Bagheri Yarmand R, Sinha K, Gururaj A, Ahmed Z, Rizvi Y, Huang S, et al. A novel dual kinase function of the RET proto-oncogene negatively regulates activating transcription factor 4-mediated apoptosis. J Biol Chem. 2015;290:11749-61 pubmed publisher
    ..RET by shRNA in medullary thyroid cancer-derived cells stimulated expression of activating transcription factor 4 (ATF4), a master transcription factor for stress-induced apoptosis, through activation of its target proapoptotic genes ..
  61. Kline C, van den Heuvel A, Allen J, Prabhu V, Dicker D, El Deiry W. ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases. Sci Signal. 2016;9:ra18 pubmed publisher TRAIL abundance and cell death through an integrated stress response (ISR) involving the transcription factor ATF4, the transactivator CHOP, and the TRAIL receptor DR5...
  62. Cho H, Cheong K, Kim H, Cheong J. Endoplasmic reticulum stress induced by hepatitis B virus X protein enhances cyclo-oxygenase 2 expression via activating transcription factor 4. Biochem J. 2011;435:431-9 pubmed publisher
    ..HBx induced the unfolded protein response and COX2 expression through the eIF2? (eukaryotic initiation factor 2?)/ATF4 (activating transcription factor 4) pathway...
  63. Han J, Jeong H, Park C, Yoon J, Ko J, Nam S, et al. Cholic acid attenuate ER stress induced cell death in coxsackievirus-B3 infection. J Microbiol Biotechnol. 2017;: pubmed publisher
    ..RT-PCR showed that the amounts of the CVB3 RNA genome and mRNA for the ER stress-related transcription factor ATF4 were significantly reduced...
  64. Ali I, Liu H, Zhong Shu L, Dong Xue M, Xu L, Shah S, et al. Reduced glutathione alleviates tunicamycin-induced endoplasmic reticulum stress in mouse preimplantation embryos. J Reprod Dev. 2017;: pubmed publisher
    ..In conclusion, GSH improves the developmental potential of mouse embryos and significantly alleviates ER stress...
  65. Teske N, Liessem A, Fischbach F, Clarner T, Beyer C, Wruck C, et al. Chemical hypoxia-induced integrated stress response activation in oligodendrocytes is mediated by the transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2). J Neurochem. 2018;144:285-301 pubmed publisher
    ..reticulum stress was monitored by the expression induction of activating transcription factor 3 and 4 (Atf3, Atf4), DNA damage-inducible transcript 3 protein (Ddit3), and glucose-regulated protein 94...
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    ..In addition, we demonstrated that PSAT1 was activated by ATF4 by chromatin immunoprecipitation (ChIP) assays...
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    ..Further, ATF6 loss delays the ERSR after SCI, potentiates PERK-ATF4-CHOP signaling and fails to improve locomotor deficits...