Genomes and Genes
activating transcription factor 4
Gene Symbol: activating transcription factor 4
Description: activating transcription factor 4
Alias: cyclic AMP-dependent transcription factor ATF-4, activating transcription factor 4 (tax-responsive enhancer element B67), activating transcription factor ATF-4, cAMP-dependent transcription factor ATF-4, rATF-4
Products: activating transcription factor 4
- Sayer J, Otto E, O Toole J, Nurnberg G, Kennedy M, Becker C, et al. The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat Genet. 2006;38:674-81 pubmed..Our findings help establish the link between centrosome function, tissue architecture and transcriptional control in the pathogenesis of cystic kidney disease, retinal degeneration, and central nervous system development. ..
- 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..Our studies resolve a mechanism responsible for inhibition of Grp78 mRNA induction by ER stress in cells that are functionally null for PERK or devoid of eIF2alpha phosphorylation. ..
- Ord D, Ord T. Mouse NIPK interacts with ATF4 and affects its transcriptional activity. Exp Cell Res. 2003;286:308-20 pubmed..Using 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...
- Wang Y, Alam G, Ning Y, Visioli F, Dong Z, Nor J, et al. The unfolded protein response induces the angiogenic switch in human tumor cells through the PERK/ATF4 pathway. Cancer Res. 2012;72:5396-406 pubmed publisher..that partially blocking UPR signaling by silencing protein kinase RNA-like ER kinase (PERK) or activating transcription factor 4 (ATF4) significantly reduced the production of angiogenesis mediators induced by GD...
- Fujinami Y, Mutai H, Kamiya K, Mizutari K, Fujii M, Matsunaga T. Enhanced expression of C/EBP homologous protein (CHOP) precedes degeneration of fibrocytes in the lateral wall after acute cochlear mitochondrial dysfunction induced by 3-nitropropionic acid. Neurochem Int. 2010;56:487-94 pubmed publisher..Quantitative real-time PCR revealed that chop and activating transcription factor 4 gene (atf-4) showed marked increase within 6h, whereas expression of other ER stress-responsive ..
- Xu B, Wang F, Wu S, Deng Y, Liu W, Feng S, et al. ?-Synuclein is involved in manganese-induced ER stress via PERK signal pathway in organotypic brain slice cultures. Mol Neurobiol. 2014;49:399-412 pubmed publisher..Moreover, alpha-synuclein protein was associated with Mn-induced activation of PERK signaling pathway. ..
- Bromati C, Lellis Santos C, Yamanaka T, Nogueira T, Leonelli M, Caperuto L, et al. UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression. Am J Physiol Regul Integr Comp Physiol. 2011;300:R92-100 pubmed publisher..day after delivery, followed by an increase in immunoglobulin heavy chain-binding protein (BiP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in islets from L3 rats...
- Edagawa M, Kawauchi J, Hirata M, Goshima H, Inoue M, Okamoto T, et al. Role of activating transcription factor 3 (ATF3) in endoplasmic reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through . J Biol Chem. 2014;289:21544-61 pubmed publisher..Both agents activated PERK-eIF2? kinases and induced the expression of activating transcription factor 4 (ATF4)-CCAAT enhancer-binding protein (C/EBP) homologous protein, which were remarkably suppressed ..
- Linares J, Cordes T, Duran A, Reina Campos M, Valencia T, Ahn C, et al. ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma. Cell Metab. 2017;26:817-829.e6 pubmed publisher..Thus, p62 directly targets nuclear transcription factors to control metabolic reprogramming in the microenvironment and repress tumorigenesis, and identifies ATF4 as a synthetic vulnerability in p62-deficient tumor stroma. ..
- Liu Z, Shi Q, Song X, Wang Y, Wang Y, Song E, et al. Activating Transcription Factor 4 (ATF4)-ATF3-C/EBP Homologous Protein (CHOP) Cascade Shows an Essential Role in the ER Stress-Induced Sensitization of Tetrachlorobenzoquinone-Challenged PC12 Cells to ROS-Mediated Apoptosis via Death Receptor 5 (DR5). Chem Res Toxicol. 2016;29:1510-8 pubmed publisher..protein kinase R-like ER kinase/eukaryotic translation initiation factor 2? (PERK/eIF2?)-mediated activating transcription factor 4 (ATF4)-ATF3-C/EBP homologous protein (CHOP) signaling pathway contributed to the process of TCBQ-..
- Jin Y, Wang L, Qu S, Sheng X, Kristian A, MÃ¦landsmo G, et al. STAMP2 increases oxidative stress and is critical for prostate cancer. EMBO Mol Med. 2015;7:315-31 pubmed publisher..Furthermore, STAMP2 effects were, at least in part, mediated by activating transcription factor 4 (ATF4), whose expression is regulated by ROS...
- Ogawa Y, Saito Y, Nishio K, Yoshida Y, Ashida H, Niki E. Gamma-tocopheryl quinone, not alpha-tocopheryl quinone, induces adaptive response through up-regulation of cellular glutathione and cysteine availability via activation of ATF4. Free Radic Res. 2008;42:674-87 pubmed publisher..An activating transcription factor 4 (ATF4)-small interfering RNA effectively attenuated the xCT mRNA level as well as the increase in ..
- 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..Collectively, the results document that CHOP is a member of the transcription factor network that controls the stress-induced regulation of specific C/EBP-ATF-containing genes, such as ASNS. ..
- Chami M, Oulès B, Szabadkai G, Tacine R, Rizzuto R, Paterlini Brechot P. Role of SERCA1 truncated isoform in the proapoptotic calcium transfer from ER to mitochondria during ER stress. Mol Cell. 2008;32:641-51 pubmed publisher..Thus, by bridging ER stress to apoptosis through increased ER-mitochondria Ca(2+) transfer, S1T acts as an essential determinant of cellular fate. ..
- Gully J, Sergeyev V, Bhootada Y, Mendez Gomez H, Meyers C, Zolotukhin S, et al. Up-regulation of activating transcription factor 4 induces severe loss of dopamine nigral neurons in a rat model of Parkinson's disease. Neurosci Lett. 2016;627:36-41 pubmed publisherb>Activating transcription factor 4 (ATF4) is a member of the PERK signaling pathway, which directly binds endoplasmic reticulum stress target genes and plays a crucial role in both adaptations to stress and activation of apoptosis...
- Konsavage W, Zhang L, Wu Y, Shenberger J. Hyperoxia-induced activation of the integrated stress response in the newborn rat lung. Am J Physiol Lung Cell Mol Physiol. 2012;302:L27-35 pubmed publisher..These findings demonstrate that Ox activates the ISR within the newborn lung and highlight regional and cell-specific alterations in the expression ISR transcription factors that regulate redox balance. ..
- Sidharthan N, Minchin R, Butcher N. Cytosolic sulfotransferase 1A3 is induced by dopamine and protects neuronal cells from dopamine toxicity: role of D1 receptor-N-methyl-D-aspartate receptor coupling. J Biol Chem. 2013;288:34364-74 pubmed publisher..Taken together, these results show that dopamine can induce its own metabolism and protect neuron-like cells from damage, suggesting that SULT1A3 activity may be a risk factor for dopamine-dependent neurodegenerative diseases. ..
- Lian N, Lin T, Liu W, Wang W, Li L, Sun S, et al. Transforming growth factor ? suppresses osteoblast differentiation via the vimentin activating transcription factor 4 (ATF4) axis. J Biol Chem. 2012;287:35975-84 pubmed publisher..Thus, our study identifies that TGF? stimulates vimentin production via PI3K-Akt-mTOR signaling, which leads to suppression of ATF4-dependent Ocn transcription and osteoblast differentiation. ..
- Duan X, Chang J, Zhang J, Zhang B, Li Y, Teng X, et al. Activating transcription factor 4 is involved in endoplasmic reticulum stress-mediated apoptosis contributing to vascular calcification. Apoptosis. 2013;18:1132-44 pubmed publisher..b>Activating transcription factor 4 (ATF4) is a critical transcription factor in osteoblastogenesis and ERS-induced apoptosis...
- Chen Y, Gui D, Chen J, He D, Luo Y, Wang N. Down-regulation of PERK-ATF4-CHOP pathway by Astragaloside IV is associated with the inhibition of endoplasmic reticulum stress-induced podocyte apoptosis in diabetic rats. Cell Physiol Biochem. 2014;33:1975-87 pubmed publisher..The protective effect of AS-IV on ER stress-induced podocyte apoptosis is associated with inhibition of PERK-ATF4-CHOP pathway. Down-regulation of PERK- ATF4-CHOP pathway by AS-IV may be a novel strategy for the treatment of DN...
- Zhang L, Zhang X, Liu C, Lu K, Huang Y, Wang Y, et al. miRNA-30a functions as a tumor suppressor by downregulating cyclin E2 expression in castration-resistant prostate cancer. Mol Med Rep. 2016;14:2077-84 pubmed publisher..The results suggest that miR?30a may function as a novel tumor suppressor in CRPC. Its anti?oncogenic activity may occur by the reduced expression of a distinct cell cycle protein, CCNE2. ..
- 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. ..
- Cho Y, Jang Y, Jang Y, Chung S, Kim H, Lee J, et al. Induction of unfolded protein response during neuronal induction of rat bone marrow stromal cells and mouse embryonic stem cells. Exp Mol Med. 2009;41:440-52 pubmed publisher..Our results showing the induction of UPR during neuronal differentiations of rBMSCs and mES cells as well as NF-L expression by ER stress inducers strongly suggest the potential role of UPR in neuronal differentiation. ..
- Ritter B, Zschüntsch J, Kvachnina E, Zhang W, Ponimaskin E. The GABA(B) receptor subunits R1 and R2 interact differentially with the activation transcription factor ATF4 in mouse brain during the postnatal development. Brain Res Dev Brain Res. 2004;149:73-7 pubmed..we demonstrate that the receptor subunits GABA(B)R1 and GABA(B)R2 interact directly with the soluble activating transcription factor 4 (ATF4) in different regions of the neonatal mouse brain...
- 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 publisherATF4 (activating transcription factor 4) is an osteoblast-enriched transcription factor that regulates terminal osteoblast differentiation and bone formation...
- 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..Thus, arsenite-induced up-regulation of VEGF gene transcription occurs by an ATF4-dependent mechanism. ..
- 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..Finally, our data indicate that targeting nutrient metabolism in energy-addicted cancers with high mTORC1 signaling may be an effective therapeutic approach. ..
- Doi T, Hara H, Kajita M, Kamiya T, Adachi T. Zinc regulates expression of IL-23 p19 mRNA via activation of eIF2Î±/ATF4 axis in HAPI cells. Biometals. 2015;28:891-902 pubmed publisher..that Zn(2+) stimulated the phosphorylation of eIF2Î± and promoted the nuclear accumulation of activating transcription factor 4 (ATF4)...
- 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 stress and oxidative ..
- Lian N, Wang W, Li L, Elefteriou F, Yang X. Vimentin inhibits ATF4-mediated osteocalcin transcription and osteoblast differentiation. J Biol Chem. 2009;284:30518-25 pubmed publisherb>Activating transcription factor 4 (ATF4) is an osteoblast-enriched transcription factor that regulates osteocalcin transcription and osteoblast terminal differentiation. To identify functional partners of ATF4, we applied ROS17/2...
- Jiang H, Wek S, McGrath B, Lu D, Hai T, Harding H, et al. Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response. Mol Cell Biol. 2004;24:1365-77 pubmed
- 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..These results suggest that the mechanism of translation reinitiation involving uORFs is conserved from yeast to mammals. ..
- 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
- Lewerenz J, Sato H, Albrecht P, Henke N, Noack R, Methner A, et al. Mutation of ATF4 mediates resistance of neuronal cell lines against oxidative stress by inducing xCT expression. Cell Death Differ. 2012;19:847-58 pubmed publisher..ATF4 mutations might have broader significance as upregulation of xCT is found in tumor cells and associated with anticancer drug resistance. ..
- Page G, Kogel D, Rangnekar V, Scheidtmann K. Interaction partners of Dlk/ZIP kinase: co-expression of Dlk/ZIP kinase and Par-4 results in cytoplasmic retention and apoptosis. Oncogene. 1999;18:7265-73 pubmed..These interactions provoked a dramatic reorganization of the cytoskeleton and morphological symptoms of apoptosis, thus suggesting a functional relationship between Dlk and Par-4 in the control of apoptosis. ..
- 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..These results indicate that ATF4 regulates basal and CdCl(2)-induced expression of the ho-1 gene in a cell-specific manner and possibly in a complex with Nrf2. ..
- 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..Collectively, the results provide both in vitro and in vivo evidence for a role of ATF4 in the transcriptional activation of the A.S. gene in response to nutrient deprivation. ..
- 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..Thus, SATB2 acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation...
- Malabanan K, Kanellakis P, Bobik A, Khachigian L. Activation transcription factor-4 induced by fibroblast growth factor-2 regulates vascular endothelial growth factor-A transcription in vascular smooth muscle cells and mediates intimal thickening in rat arteries following balloon injury. Circ Res. 2008;103:378-87 pubmed publisher..These findings reveal, for the first time, the induction of ATF-4 by both vascular injury and FGF-2. ATF-4 serves as a conduit for the inducible expression of 1 growth factor by another during the process of intimal thickening. ..
- Dong L, Guarino B, Jordan Sciutto K, Winkelstein B. Activating transcription factor 4, a mediator of the integrated stress response, is increased in the dorsal root ganglia following painful facet joint distraction. Neuroscience. 2011;193:377-86 pubmed publisher..These behavioral and immunohistochemical findings imply that facet-mediated pain may be sustained through other pathways of the ISR. ..
- 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..Our study establishes that leptin-regulated neural pathways control both aspects of bone remodelling, and demonstrates that integrity of sympathetic signalling is necessary for the increase in bone resorption caused by gonadal failure. ..
- Zhang A, Zhang J, Sun P, Yao C, Su C, Sui T, et al. EIF2alpha and caspase-12 activation are involved in oxygen-glucose-serum deprivation/restoration-induced apoptosis of spinal cord astrocytes. Neurosci Lett. 2010;478:32-6 pubmed publisher..ER stress kinase (PERK), p-PERK, eukaryotic initiation factor 2 alpha (eIF2 alpha), p-eIF2 alpha, activating transcription factor 4 (ATF4), caspase-12, were examined...
- Koyanagi S, Hamdan A, Horiguchi M, Kusunose N, Okamoto A, Matsunaga N, et al. cAMP-response element (CRE)-mediated transcription by activating transcription factor-4 (ATF4) is essential for circadian expression of the Period2 gene. J Biol Chem. 2011;286:32416-23 pubmed publisher..These results suggest that ATF4 is a component responsible for sustaining circadian oscillation of CRE-mediated gene expression and also constitute a molecular link connecting cAMP-dependent signaling to the circadian clock. ..
- Wang S, Kaufman R. The impact of the unfolded protein response on human disease. J Cell Biol. 2012;197:857-67 pubmed publisher..Signaling components of the UPR are emerging as potential targets for intervention and treatment of human disease. ..
- Page G, Lödige I, Kogel D, Scheidtmann K. AATF, a novel transcription factor that interacts with Dlk/ZIP kinase and interferes with apoptosis. FEBS Lett. 1999;462:187-91 pubmed..Indeed, a Gal4-BD-AATF fusion protein exhibited strong transactivation activity. Interestingly, AATF interfered with Dlk-induced apoptosis. ..
- Ambivero C, Cilenti L, Zervos A. ATF4 interacts with Abro1/KIAA0157 scaffold protein and participates in a cytoprotective pathway. Biochim Biophys Acta. 2012;1823:2149-56 pubmed publisher..This regulation involves the participation of at least three known members of the AP-1 family of transcription factors. ..
- 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..These results demonstrated that ATF4 is essential for the later stages of lens fibre cell differentiation. ..