Gene Symbol: Atf4
Description: activating transcription factor 4
Alias: Atf-4, C/ATF, CREB2, TAXREB67, cyclic AMP-dependent transcription factor ATF-4, c/EBP-related ATF, cAMP-dependent transcription factor ATF-4, tax-responsive enhancer element-binding protein 67 homolog, taxREB67 homolog
Species: mouse
Products:     Atf4

Top Publications

  1. Yoshizawa T, Hinoi E, Jung D, Kajimura D, Ferron M, Seo J, et al. The transcription factor ATF4 regulates glucose metabolism in mice through its expression in osteoblasts. J Clin Invest. 2009;119:2807-17 pubmed publisher
    ..Activating transcription factor 4 (ATF4) is a transcription factor that accumulates predominantly in osteoblasts, where it regulates virtually all ..
  2. 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...
  3. Li H, Meng Q, Xiao F, Chen S, Du Y, Yu J, et al. ATF4 deficiency protects mice from high-carbohydrate-diet-induced liver steatosis. Biochem J. 2011;438:283-9 pubmed publisher
    ..b>ATF4 (activating transcription factor 4) has been shown to play an important role in the regulation of glucose ..
  4. Han J, Back S, Hur J, Lin Y, Gildersleeve R, Shan J, et al. ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nat Cell Biol. 2013;15:481-90 pubmed publisher
    ..ChIP-seq and mRNA-seq of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), key transcription factors downstream of p-eIF2?, demonstrated that they ..
  5. Yadav V, Ryu J, Suda N, Tanaka K, Gingrich J, Schutz G, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 2008;135:825-37 pubmed publisher
    ..By identifying duodenum-derived serotonin as a hormone inhibiting bone formation in an Lrp5-dependent manner, this study broadens our understanding of bone remodeling and suggests potential therapies to increase bone mass. ..
  6. Lange P, Chavez J, Pinto J, Coppola G, Sun C, Townes T, et al. ATF4 is an oxidative stress-inducible, prodeath transcription factor in neurons in vitro and in vivo. J Exp Med. 2008;205:1227-42 pubmed publisher
    ..vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons...
  7. Vallejo M, Ron D, Miller C, Habener J. C/ATF, a member of the activating transcription factor family of DNA-binding proteins, dimerizes with CAAT/enhancer-binding proteins and directs their binding to cAMP response elements. Proc Natl Acad Sci U S A. 1993;90:4679-83 pubmed
  8. Wang X, Wang G, Kunte M, Shinde V, Gorbatyuk M. Modulation of angiogenesis by genetic manipulation of ATF4 in mouse model of oxygen-induced retinopathy [corrected]. Invest Ophthalmol Vis Sci. 2013;54:5995-6002 pubmed publisher
    The activation of the unfolded protein response (UPR) and an increase in activating transcription factor 4 (ATF4) has been previously reported in the diabetic retina...
  9. Costa Mattioli M, Gobert D, Stern E, Gamache K, Colina R, Cuello C, et al. eIF2alpha phosphorylation bidirectionally regulates the switch from short- to long-term synaptic plasticity and memory. Cell. 2007;129:195-206 pubmed
    ..Phosphorylation of eIF2alpha inhibits general translation but selectively stimulates translation of ATF4, a repressor of CREB-mediated late-LTP (L-LTP) and LTM...

More Information


  1. Saito A, Hino S, Murakami T, Kanemoto S, Kondo S, Saitoh M, et al. Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis. Nat Cell Biol. 2009;11:1197-204 pubmed publisher
    ..Our findings provide a new link by which ER stress is converted to signalling for the activation of ER-to-Golgi trafficking. ..
  2. Seo J, Fortuno E, Suh J, Stenesen D, Tang W, Parks E, et al. Atf4 regulates obesity, glucose homeostasis, and energy expenditure. Diabetes. 2009;58:2565-73 pubmed publisher
    We evaluate a potential role of activating transcription factor 4 (Atf4) in invertebrate and mammalian metabolism. With two parallel approaches-a fat body-specific green fluorescent protein enhancer trap screen in D...
  3. Wang W, Lian N, Li L, Moss H, Wang W, Perrien D, et al. Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription. Development. 2009;136:4143-53 pubmed publisher
    Activating transcription factor 4 (Atf4) is a leucine-zipper-containing protein of the cAMP response element-binding protein (CREB) family...
  4. Harding H, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell. 2000;6:1099-108 pubmed
    ..GCN2 repress translation of most mRNAs but selectively increase translation of Activating Transcription Factor 4 (ATF4), resulting in the induction of the downstream gene CHOP (GADD153)...
  5. Zhang X, Yu S, Galson D, Luo M, Fan J, Zhang J, et al. Activating transcription factor 4 is critical for proliferation and survival in primary bone marrow stromal cells and calvarial osteoblasts. J Cell Biochem. 2008;105:885-95 pubmed publisher
    Activating transcription factor 4 (ATF4) is essential for bone formation. However, the mechanism of its actions in bone is poorly understood...
  6. 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 ..
  7. Bruhat A, Cherasse Y, Maurin A, Breitwieser W, Parry L, Deval C, et al. ATF2 is required for amino acid-regulated transcription by orchestrating specific histone acetylation. Nucleic Acids Res. 2007;35:1312-21 pubmed
    ..acid deprivation involves the activating transcription factor 2 (ATF2) and the activating transcription factor 4 (ATF4) binding the amino acid response element (AARE) within the promoter...
  8. Zhu K, Jiao H, Li S, Cao H, Galson D, Zhao Z, et al. ATF4 promotes bone angiogenesis by increasing VEGF expression and release in the bone environment. J Bone Miner Res. 2013;28:1870-1884 pubmed publisher
    Activating transcription factor 4 (ATF4) is a critical transcription factor for bone remodeling; however, its role in bone angiogenesis has not been established...
  9. 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...
  10. Tanaka T, Tsujimura T, Takeda K, Sugihara A, Maekawa A, Terada N, et al. Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres. Genes Cells. 1998;3:801-10 pubmed
    Activating transcription factor-4 (ATF4)--also termed CREB2, C/ATF, and TAXREB67--is a basic-leucine zipper (bZip) transcription factor that belongs to the ATF/CREB family...
  11. Nehring R, Horikawa H, El Far O, Kneussel M, Brandstätter J, Stamm S, et al. The metabotropic GABAB receptor directly interacts with the activating transcription factor 4. J Biol Chem. 2000;275:35185-91 pubmed
    ..Thus, inhibitory metabotropic GABA(B)Rs may regulate activity-dependent gene expression via a direct interaction with ATF-4. ..
  12. Xiao G, Jiang D, Ge C, Zhao Z, Lai Y, Boules H, et al. Cooperative interactions between activating transcription factor 4 and Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression. J Biol Chem. 2005;280:30689-96 pubmed
    The role of ATF4 (activating transcription factor 4) in osteoblast differentiation and bone formation was recently described using ATF4-deficient mice (Yang, X., Matsuda, K., Bialek, P., Jacquot, S., Masuoka, H. C., Schinke, T., Li, L...
  13. Zhang Q, Yu J, Liu B, Lv Z, Xia T, Xiao F, et al. Central activating transcription factor 4 (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve. Diabetes. 2013;62:2230-9 pubmed publisher
    ..of our current study is to investigate the possible involvement of hypothalamic activating transcription factor 4 (ATF4) in the regulation of insulin sensitivity in the liver...
  14. Bagheri Yarmand R, Vadlamudi R, Kumar R. Activating transcription factor 4 overexpression inhibits proliferation and differentiation of mammary epithelium resulting in impaired lactation and accelerated involution. J Biol Chem. 2003;278:17421-9 pubmed
    ..In this study, we sought to determine specifically the consequences of ATF4 expression on mammary gland development in transgenic mice...
  15. Ma Y, Hendershot L. Delineation of a negative feedback regulatory loop that controls protein translation during endoplasmic reticulum stress. J Biol Chem. 2003;278:34864-73 pubmed
    ..We show that activating transcription factor-4 (ATF4), which is paradoxically translated during the eIF-2 alpha-mediated translational block, is required for the ..
  16. Elefteriou F, Benson M, Sowa H, Starbuck M, Liu X, Ron D, et al. ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae. Cell Metab. 2006;4:441-51 pubmed
    The transcription factor ATF4 enhances bone formation by favoring amino acid import and collagen synthesis in osteoblasts, a function requiring its phosphorylation by RSK2, the kinase inactivated in Coffin-Lowry Syndrome...
  17. Hettmann T, Barton K, Leiden J. Microphthalmia due to p53-mediated apoptosis of anterior lens epithelial cells in mice lacking the CREB-2 transcription factor. Dev Biol. 2000;222:110-23 pubmed
    CREB-2 (also called ATF4, TAXREB67, or C/ATF) is an evolutionarily conserved member of the CREB/ATF family of basic-leucine zipper transcription factors...
  18. 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...
  19. Cherasse Y, Maurin A, Chaveroux C, Jousse C, Carraro V, Parry L, et al. The p300/CBP-associated factor (PCAF) is a cofactor of ATF4 for amino acid-regulated transcription of CHOP. Nucleic Acids Res. 2007;35:5954-65 pubmed triggered that leads to increased translation of the 'master regulator', activating transcription factor 4 (ATF4), and resulting in the induction of specific target genes...
  20. Harding H, Zhang Y, Zeng H, Novoa I, Lu P, Calfon M, et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell. 2003;11:619-33 pubmed
    ..inhibits general protein synthesis while promoting translation and expression of the transcription factor ATF4. Atf4(-/-) cells are impaired in expressing genes involved in amino acid import, glutathione biosynthesis, and ..
  21. Yu S, Franceschi R, Luo M, Fan J, Jiang D, Cao H, et al. Critical role of activating transcription factor 4 in the anabolic actions of parathyroid hormone in bone. PLoS ONE. 2009;4:e7583 pubmed publisher
    ..impaired in both growing and adult ovariectomized mice lacking bone-related activating transcription factor 4 (ATF4)...
  22. Vidal R, Figueroa A, Court F, Thielen P, Molina C, Wirth C, et al. Targeting the UPR transcription factor XBP1 protects against Huntington's disease through the regulation of FoxO1 and autophagy. Hum Mol Genet. 2012;21:2245-62 pubmed publisher
    ..contribution of ER stress to HD by targeting the expression of two main UPR transcription factors, XBP1 and ATF4 (activating transcription factor 4), in full-length mutant Huntingtin (mHtt) transgenic mice...
  23. 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 ..
  24. Masuoka H, Townes T. Targeted disruption of the activating transcription factor 4 gene results in severe fetal anemia in mice. Blood. 2002;99:736-45 pubmed
    ..To determine the in vivo function of ATF4, the ATF4 gene in murine embryonic stem cells was deleted and homozygous mutant mice were generated...
  25. Cao H, Yu S, Yao Z, Galson D, Jiang Y, Zhang X, et al. Activating transcription factor 4 regulates osteoclast differentiation in mice. J Clin Invest. 2010;120:2755-66 pubmed publisher
    Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established...
  26. Chevray P, Nathans D. Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun. Proc Natl Acad Sci U S A. 1992;89:5789-93 pubmed
    ..One of these is a bZIP protein of the ATF/CREB protein family--probably the murine homolog of TAXREB67. Two others encode polypeptides with predicted potential to form coiled-coil structures, and seven other isolates ..
  27. Yu S, Franceschi R, Luo M, Zhang X, Jiang D, Lai Y, et al. Parathyroid hormone increases activating transcription factor 4 expression and activity in osteoblasts: requirement for osteocalcin gene expression. Endocrinology. 2008;149:1960-8 pubmed publisher
    ..2 promoter through the osteoblast-specific element 1 site, a recently identified activating transcription factor-4 (ATF4) -binding element...
  28. Rutkowski D, Arnold S, Miller C, Wu J, Li J, Gunnison K, et al. Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLoS Biol. 2006;4:e374 pubmed
    ..It underscores the contribution of posttranscriptional and posttranslational mechanisms in influencing this outcome. ..
  29. Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Farinas I, et al. SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell. 2006;125:971-86 pubmed
    ..Molecular analysis revealed that SATB2 directly interacts with and enhances the activity of both Runx2 and ATF4, transcription factors that regulate osteoblast differentiation...
  30. Elefteriou F, Ahn J, Takeda S, Starbuck M, Yang X, Liu X, et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature. 2005;434:514-20 pubmed
    ..This sympathetic function requires phosphorylation (by protein kinase A) of ATF4, a cell-specific CREB-related transcription factor essential for osteoblast differentiation and function...
  31. 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...
  32. Lewerenz J, Maher P. Basal levels of eIF2alpha phosphorylation determine cellular antioxidant status by regulating ATF4 and xCT expression. J Biol Chem. 2009;284:1106-15 pubmed publisher
    ..The mechanistic link between the absence of phospho-eIF2alpha and xCT expression is nuclear factor ATF4. Consistent with these findings, long term activation of the phospho-eIF2alpha/ATF4/xCT signaling module by the ..
  33. Oyadomari S, Harding H, Zhang Y, Oyadomari M, Ron D. Dephosphorylation of translation initiation factor 2alpha enhances glucose tolerance and attenuates hepatosteatosis in mice. Cell Metab. 2008;7:520-32 pubmed publisher
    ..These observations suggest that eIF2(alphaP)-mediated translation of key hepatic transcriptional regulators of intermediary metabolism contributes to the detrimental consequences of nutrient excess. ..
  34. Yang X, Karsenty G. ATF4, the osteoblast accumulation of which is determined post-translationally, can induce osteoblast-specific gene expression in non-osteoblastic cells. J Biol Chem. 2004;279:47109-14 pubmed
    Based on the analysis of a loss-of-function model, we recently showed that ATF4 regulates osteoblast terminal differentiation and function and is implicated in the pathophysiology of Coffin-Lowry syndrome...
  35. Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka H, Schinke T, et al. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Cell. 2004;117:387-98 pubmed
    ..We identify the transcription factor ATF4 as a critical substrate of RSK2 that is required for the timely onset of osteoblast differentiation, for terminal ..
  36. Wang C, Huang Z, Du Y, Cheng Y, Chen S, Guo F. ATF4 regulates lipid metabolism and thermogenesis. Cell Res. 2010;20:174-84 pubmed publisher
    Activating transcription factor 4 (ATF4) has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism...
  37. Ord D, Ord T. Mouse NIPK interacts with ATF4 and affects its transcriptional activity. Exp Cell Res. 2003;286:308-20 pubmed
    ..the yeast two-hybrid screening of an embryonic mouse cDNA library, we identified activating transcription factor 4 (ATF4) as a protein binding to mouse (m) NIPK...
  38. Galehdar Z, Swan P, Fuerth B, Callaghan S, Park D, Cregan S. Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA. J Neurosci. 2010;30:16938-48 pubmed publisher
    ..and cell death through a p53-independent mechanism mediated by the ER-stress-inducible transcription factor ATF4 (activating transcription factor 4)...
  39. Kajimura D, Hinoi E, Ferron M, Kode A, Riley K, Zhou B, et al. Genetic determination of the cellular basis of the sympathetic regulation of bone mass accrual. J Exp Med. 2011;208:841-51 pubmed publisher
    ..cAMP-responsive element-binding protein) phosphorylation and thus decrease osteoblast proliferation and to promote ATF4 phosphorylation and thus increase RANKL (receptor activator of NF-?B ligand) expression, which then stimulates ..
  40. Yu S, Jiang Y, Galson D, Luo M, Lai Y, Lu Y, et al. General transcription factor IIA-gamma increases osteoblast-specific osteocalcin gene expression via activating transcription factor 4 and runt-related transcription factor 2. J Biol Chem. 2008;283:5542-53 pubmed publisher
    b>ATF4 (activating transcription factor 4) is an osteoblast-enriched transcription factor that regulates terminal osteoblast differentiation and bone formation...
  41. 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 ..
  42. Khan I, Tang E, Arany P. Molecular pathway of near-infrared laser phototoxicity involves ATF-4 orchestrated ER stress. Sci Rep. 2015;5:10581 pubmed publisher
    ..This study outlines the mechanism of NIR laser phototoxicity and the utility of monitoring surface temperature and ATF4 expression as potential biomarkers to develop safe and effective clinical applications.
  43. Wan X, Lu X, Xiao Y, Lin Y, Zhu H, Ding T, et al. ATF4- and CHOP-dependent induction of FGF21 through endoplasmic reticulum stress. Biomed Res Int. 2014;2014:807874 pubmed publisher
    ..FGF21 is the target gene for activating transcription factor 4 (ATF4) and CCAAT enhancer binding protein homologous protein (CHOP)...
  44. Liu M, Xia Y, Ding J, Ye B, Zhao E, Choi J, et al. Transcriptional Profiling Reveals a Common Metabolic Program in High-Risk Human Neuroblastoma and Mouse Neuroblastoma Sphere-Forming Cells. Cell Rep. 2016;17:609-623 pubmed publisher
    ..synthesis pathways, primarily as a result of increased expression of sterol regulatory element binding factors and Atf4, respectively...
  45. Firtina Z, Danysh B, Bai X, Gould D, Kobayashi T, Duncan M. Abnormal expression of collagen IV in lens activates unfolded protein response resulting in cataract. J Biol Chem. 2009;284:35872-84 pubmed publisher
    ..Collectively, the results provide in vivo evidence for a role of UPR in cataract formation in response to accumulation of terminally unfolded proteins in the endoplasmic reticulum. ..
  46. Malabanan K, Sheahan A, Khachigian L. Platelet-derived growth factor-BB mediates cell migration through induction of activating transcription factor 4 and tenascin-C. Am J Pathol. 2012;180:2590-7 pubmed publisher
    ..Our findings thus demonstrate the role of ATF-4 in both injury- and PDGF-BB-inducible TN-C expression and cell migration. ..
  47. Pasini S, Corona C, Liu J, Greene L, Shelanski M. Specific downregulation of hippocampal ATF4 reveals a necessary role in synaptic plasticity and memory. Cell Rep. 2015;11:183-91 pubmed
    Prior studies suggested that the transcription factor ATF4 negatively regulates synaptic plastic and memory...
  48. Tanaka K, Kaji H, Yamaguchi T, Kanazawa I, Canaff L, Hendy G, et al. Involvement of the osteoinductive factors, Tmem119 and BMP-2, and the ER stress response PERK-eIF2?-ATF4 pathway in the commitment of myoblastic into osteoblastic cells. Calcif Tissue Int. 2014;94:454-64 pubmed publisher
    ..In the present study, we examined the relationship among BMP-2, Tmem119, and the PERK-eIF2?-ATF4 endoplasmic reticulum (ER) stress response pathway in the differentiation of C2C12 myoblasts into osteoblastic ..
  49. Chan S, Zhao X, Elfowiris A, Ratnam C, Herbert T. The role of de novo protein synthesis and SIRT1 in ER stress-induced Atf4 and Chop mRNA expression in mammalian cells. Biochimie. 2017;138:156-167 pubmed publisher
    ..This is promoted by activating transcription factor 4 (ATF4) whose expression is rapidly up-regulated in response to ER stress through an eIF2? phosphorylation-dependent ..
  50. Li W, Li X, Miller R. ATF4 activity: a common feature shared by many kinds of slow-aging mice. Aging Cell. 2014;13:1012-8 pubmed publisher
    b>ATF4, a DNA-binding factor that modulates responses to amino acid availability and ribosomal function, has been shown to be altered in both liver and fibroblasts from two strains of long-lived mice, i.e...
  51. Khavandgar Z, Poirier C, Clarke C, Li J, WANG N, McKee M, et al. A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization. J Cell Biol. 2011;194:277-89 pubmed publisher
    ..Our data suggest tissue-specific roles for nSMase2 in skeletal tissues. ..
  52. Csibi A, Fendt S, Li C, Poulogiannis G, Choo A, Chapski D, et al. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell. 2013;153:840-54 pubmed publisher
    ..mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2 (CREB2). Thus, a relationship between mTORC1, SIRT4, and cancer is suggested by our findings...
  53. Soda T, Frank C, Ishizuka K, Baccarella A, Park Y, Flood Z, et al. DISC1-ATF4 transcriptional repression complex: dual regulation of the cAMP-PDE4 cascade by DISC1. Mol Psychiatry. 2013;18:898-908 pubmed publisher
    ..DISC1 interacts with numerous proteins that impact neuronal function, including activating transcription factor 4 (ATF4)...
  54. Obri A, Makinistoglu M, Zhang H, Karsenty G. HDAC4 integrates PTH and sympathetic signaling in osteoblasts. J Cell Biol. 2014;205:771-80 pubmed publisher
    ..cyclic adenosine monophosphate production through an unidentified transcription factor for PTH and through ATF4 for the sympathetic tone...
  55. Nishizawa M, Nagata S. cDNA clones encoding leucine-zipper proteins which interact with G-CSF gene promoter element 1-binding protein. FEBS Lett. 1992;299:36-8 pubmed
    ..Three leucine-zipper proteins were isolated from mouse cDNA expression libraries by this method: NF-IL6, ATF4, and a novel ATF4-related ATFx...
  56. Takahata Y, Hinoi E, Takarada T, Nakamura Y, Ogawa S, Yoneda Y. Positive regulation by ?-aminobutyric acid B receptor subunit-1 of chondrogenesis through acceleration of nuclear translocation of activating transcription factor-4. J Biol Chem. 2012;287:33293-303 pubmed
    ..of GABA(B)R1 led to synergistic promotion of the transcriptional activity of activating transcription factor-4 (ATF4) essential for normal chondrogenesis, in addition to facilitating ATF4-dependent Ihh promoter activation...
  57. Shum E, Jones S, Shao A, Dumdie J, Krause M, Chan W, et al. The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay. Cell. 2016;165:382-95 pubmed publisher
    ..Mice conditionally lacking UPF3A exhibit "hyper" NMD and display defects in embryogenesis and gametogenesis. Our results support a model in which UPF3A serves as a molecular rheostat that directs developmental events. ..
  58. Masuda M, Miyazaki Anzai S, Keenan A, Shiozaki Y, Okamura K, Chick W, et al. Activating transcription factor-4 promotes mineralization in vascular smooth muscle cells. JCI Insight. 2016;1:e88646 pubmed
    Emerging evidence indicates that upregulation of the ER stress-induced pro-osteogenic transcription factor ATF4 plays an important role in vascular calcification, a common complication in patients with aging, diabetes, and chronic kidney ..
  59. 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 ..
  60. Iwasaki Y, Suganami T, Hachiya R, Shirakawa I, Kim Saijo M, Tanaka M, et al. Activating transcription factor 4 links metabolic stress to interleukin-6 expression in macrophages. Diabetes. 2014;63:152-61 pubmed publisher
    ..DNA microarray analysis using primary macrophages revealed that the ATF4 pathway is activated by SFAs...
  61. Horiguchi M, Koyanagi S, Hamdan A, Kakimoto K, Matsunaga N, Yamashita C, et al. Rhythmic control of the ARF-MDM2 pathway by ATF4 underlies circadian accumulation of p53 in malignant cells. Cancer Res. 2013;73:2639-49 pubmed publisher
    ..In this study, we show that the transcription factor ATF4, a component of the mammalian circadian clock, functions in circadian accumulation of p53 protein in tumor cells...
  62. Yamaguchi S, Ishihara H, Yamada T, Tamura A, Usui M, Tominaga R, et al. ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress. Cell Metab. 2008;7:269-76 pubmed publisher
    ..The Eif4ebp1 gene encoding 4E-BP1 was revealed to be a direct target of the transcription factor ATF4. Deletion of the Eif4ebp1 gene increased susceptibility to ER stress-mediated apoptosis in MIN6 beta cells and ..
  63. Wang C, Xia T, Du Y, Meng Q, Li H, Liu B, et al. Effects of ATF4 on PGC1? expression in brown adipose tissue and metabolic responses to cold stress. Metabolism. 2013;62:282-9 pubmed publisher
    ..PGC1?) increases significantly in the white and brown adipose tissue of activating transcription factor 4 (ATF4) global knockout mice, which suggests that ATF4 is involved in the regulation of PGC1? expression...
  64. Li K, Xiao Y, Yu J, Xia T, Liu B, Guo Y, et al. Liver-specific Gene Inactivation of the Transcription Factor ATF4 Alleviates Alcoholic Liver Steatosis in Mice. J Biol Chem. 2016;291:18536-46 pubmed publisher
    Although numerous biological functions of the activating transcription factor 4 (ATF4) have been identified, a direct effect of ATF4 on alcoholic liver steatosis has not been described previously...
  65. Wang W, Lian N, Ma Y, Li L, Gallant R, Elefteriou F, et al. Chondrocytic Atf4 regulates osteoblast differentiation and function via Ihh. Development. 2012;139:601-11 pubmed publisher
    b>Atf4 is a leucine zipper-containing transcription factor that activates osteocalcin (Ocn) in osteoblasts and indian hedgehog (Ihh) in chondrocytes...
  66. Thevenot P, Sierra R, Raber P, Al Khami A, Trillo Tinoco J, Zarreii P, et al. The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors. Immunity. 2014;41:389-401 pubmed publisher
    ..IL-6 overexpression restored immune-suppressive activity of Chop-deficient MDSCs. These findings suggest the role of Chop in tumor-induced tolerance and the therapeutic potential of targeting Chop in MDSCs for cancer immunotherapy. ..