Gene Symbol: Atf2
Description: activating transcription factor 2
Alias: cyclic AMP-dependent transcription factor ATF-2, cAMP response element-binding protein CRE-BP1, cAMP-dependent transcription factor ATF-2
Species: rat
Products:     Atf2

Top Publications

  1. Gueorguiev V, Cheng S, Sabban E. Prolonged activation of cAMP-response element-binding protein and ATF-2 needed for nicotine-triggered elevation of tyrosine hydroxylase gene transcription in PC12 cells. J Biol Chem. 2006;281:10188-95 pubmed
    ..The results suggest that both ATF-2 and CREB mediate activation of TH gene transcription by nicotine. ..
  2. Howe G, Kazda K, Addison C. MicroRNA-30b controls endothelial cell capillary morphogenesis through regulation of transforming growth factor beta 2. PLoS ONE. 2017;12:e0185619 pubmed publisher
    ..Up-regulation of TGF?2 by miR-30b overexpression was found to be dependent on ATF2 activation, a transcription factor known to regulate TGF?2 expression, as miR-30b overexpressing cells exhibited ..
  3. Martin Villalba A, Winter C, Brecht S, Buschmann T, Zimmermann M, Herdegen T. Rapid and long-lasting suppression of the ATF-2 transcription factor is a common response to neuronal injury. Brain Res Mol Brain Res. 1998;62:158-66 pubmed
  4. Hai T, Liu F, Coukos W, Green M. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989;3:2083-90 pubmed
    ..Our results help to explain how a single promoter element, an ATF site, can be present in a wide variety of promoters. ..
  5. Kageyama R, Sasai Y, Nakanishi S. Molecular characterization of transcription factors that bind to the cAMP responsive region of the substance P precursor gene. cDNA cloning of a novel C/EBP-related factor. J Biol Chem. 1991;266:15525-31 pubmed
    ..We find that a novel factor and ATF2 bind to the region containing the CRE of the substance P precursor gene...
  6. Green T, Alibhai I, Unterberg S, Neve R, Ghose S, Tamminga C, et al. Induction of activating transcription factors (ATFs) ATF2, ATF3, and ATF4 in the nucleus accumbens and their regulation of emotional behavior. J Neurosci. 2008;28:2025-32 pubmed publisher
    ..We demonstrate here that ATF2, ATF3, and ATF4 are each robustly induced in the nucleus accumbens and dorsal striatum by restraint stress or by ..
  7. Kodeboyina S, Balamurugan P, Liu L, Pace B. cJun modulates Ggamma-globin gene expression via an upstream cAMP response element. Blood Cells Mol Dis. 2010;44:7-15 pubmed publisher
    ..We conclude that these data indicate that cJun activates the Ggamma-globin promoter via the G-CRE in a manner comparable with CREB1 and propose a model for gamma-globin activation based on DNA-protein interactions in the G-CRE. ..
  8. Zhou W, Lin L, Majumdar A, Li X, Zhang X, Liu W, et al. Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2. Nat Genet. 2007;39:1225-34 pubmed
    ..Thus, we propose that transcriptional readout mediated at least in part by a Wnt11 --> ATF/CREB --> TGFbeta2 pathway is critical in regulating morphogenesis in response to noncanonical Wnt signaling. ..
  9. Levkovitch Verbin H, Harizman N, Dardik R, Nisgav Y, Vander S, Melamed S. Regulation of cell death and survival pathways in experimental glaucoma. Exp Eye Res. 2007;85:250-8 pubmed
    ..We conclude that retinal ganglion cell death in glaucoma involves activation, at different time points, of multiple pro-apoptotic pathways (the MAP kinase pathway and the caspase family) and pro-survival (PI-3 Kinase/ Akt and p-ERK). ..

More Information


  1. Nishikawa S. Transient increase in anti-p-ATF2 immunoreactivity in the late secretion ameloblasts apical to the transition zone of rat incisors. Anat Sci Int. 2004;79:87-94 pubmed
    Activating transcription factor 2 (ATF2) was localized in the ameloblasts of rat incisors by immunohistochemistry...
  2. Gong P, Stewart D, Hu B, Vinson C, Alam J. Multiple basic-leucine zipper proteins regulate induction of the mouse heme oxygenase-1 gene by arsenite. Arch Biochem Biophys. 2002;405:265-74 pubmed
    ..MafG, ATF2, FosB, and JunB were also detected in the arsenite complex...
  3. Bhoumik A, Singha N, O Connell M, Ronai Z. Regulation of TIP60 by ATF2 modulates ATM activation. J Biol Chem. 2008;283:17605-14 pubmed publisher
    ..Here we show that under non-stressed conditions, activating transcription factor-2 (ATF2) in cooperation with Cul3 ubiquitin ligase promotes degradation of TIP60, thereby attenuating its HAT activity...
  4. Ribas V, Arruda Carvalho M, Linden R, Chiarini L. Early c-Jun N-terminal kinase-dependent phosphorylation of activating transcription factor-2 is associated with degeneration of retinal ganglion cells. Neuroscience. 2011;180:64-74 pubmed publisher
    ..Finally, the inhibitor of JNK blocked the upregulation of both c-Jun and Hrk in the GCL after retinal explantation. The data show that phosphorylation of ATF-2 by JNK is associated with retinal ganglion cell death after axon damage. ..
  5. Robert K, Santiard Baron D, Chassé J, Paly E, Aupetit J, Kamoun P, et al. The neuronal SAPK/JNK pathway is altered in a murine model of hyperhomocysteinemia. J Neurochem. 2004;89:33-43 pubmed
    ..JNK and c-Jun were activated in the hippocampal neurones of CBS-deficient mice, suggesting that the SAPK/JNK pathway may play an important role in the development of neuronal defects associated with hyperhomocysteinemia. ..
  6. Suzuki T, Yamakuni T, Hagiwara M, Ichinose H. Identification of ATF-2 as a transcriptional regulator for the tyrosine hydroxylase gene. J Biol Chem. 2002;277:40768-74 pubmed
  7. Rauch A, Rosskothen Kuhl N, Illing R. Counter-regulation of the AP-1 monomers pATF2 and Fos: Molecular readjustment of brainstem neurons in hearing and deaf adult rats after electrical intracochlear stimulation. Neuroscience. 2016;313:184-98 pubmed publisher
    ..of the immediate-early gene fos (also known as c-fos) and phosphorylation of the product of the early response gene atf2 (pATF2) in the adult auditory brainstem can be modulated by electrical intracochlear stimulation...
  8. Pejchal J, Osterreicher J, Vilasová Z, Tichy A, Vavrova J. Expression of activated ATF-2, CREB and c-Myc in rat colon transversum after whole-body gamma-irradiation and its contribution to pathogenesis and biodosimetry. Int J Radiat Biol. 2008;84:315-24 pubmed publisher
    ..The detection of p-ATF-2 and p-CREB might be considered as a perspective biodosimetric tool for irradiated enterocytes in vivo. The use of p-c-Myc appears to be controversial due to the ambivalent expression values. ..
  9. Bhoumik A, Takahashi S, Breitweiser W, Shiloh Y, Jones N, RONAI Z. ATM-dependent phosphorylation of ATF2 is required for the DNA damage response. Mol Cell. 2005;18:577-87 pubmed
    Activating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines 490 and 498 following ionizing radiation (IR)...
  10. Lu G, Kang Y, Han J, Herschman H, Stefani E, Wang Y. TAB-1 modulates intracellular localization of p38 MAP kinase and downstream signaling. J Biol Chem. 2006;281:6087-95 pubmed
    ..These results suggest a previously unknown mechanism for stress-MAP kinase regulation in mammalian cells. ..
  11. de França S, dos Santos M, Przygodda F, Garófalo M, Kettelhut I, Magalhães D, et al. A Low-Protein, High-Carbohydrate Diet Stimulates Thermogenesis in the Brown Adipose Tissue of Rats via ATF-2. Lipids. 2016;51:303-10 pubmed publisher
    ..Our results suggest that the increase in UCP1 content may occur via p38 MAPK and ATF2.
  12. Yuan Z, Gong S, Luo J, Zheng Z, Song B, Ma S, et al. Opposing roles for ATF2 and c-Fos in c-Jun-mediated neuronal apoptosis. Mol Cell Biol. 2009;29:2431-42 pubmed publisher
    ..that c-Jun-mediated neuronal apoptosis requires the concomitant activation of activating transcription factor-2 (ATF2) and downregulation of c-Fos...
  13. Kyosseva S, Elbein A, Hutton T, Griffin S, Mrak R, Sturner W, et al. Increased levels of transcription factors Elk-1, cyclic adenosine monophosphate response element-binding protein, and activating transcription factor 2 in the cerebellar vermis of schizophrenic patients. Arch Gen Psychiatry. 2000;57:685-91 pubmed
  14. Maekawa T, Jin W, Ishii S. The role of ATF-2 family transcription factors in adipocyte differentiation: antiobesity effects of p38 inhibitors. Mol Cell Biol. 2010;30:613-25 pubmed publisher
    ..In p38 inhibitor-treated mice, macrophage infiltration into WAT was reduced and the tumor necrosis factor alpha (TNF-alpha) levels were lower than control mice. Thus, p38 inhibitors may provide a novel antiobesity treatment. ..
  15. Kawasaki H, Schiltz L, Chiu R, Itakura K, Taira K, Nakatani Y, et al. ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation. Nature. 2000;405:195-200 pubmed
    ..ATF-2 may represent a new class of sequence-specific factors, which are able to activate transcription by direct effects on chromatin components. ..
  16. Wei Y, Jiang J, Sun M, Chen X, Wang H, Gu J. ATF5 increases cisplatin-induced apoptosis through up-regulation of cyclin D3 transcription in HeLa cells. Biochem Biophys Res Commun. 2006;339:591-6 pubmed
    ..Taken together, these results suggest that ATF5 increases cisplatin-induced apoptosis through up-regulation of Cyclin D3 transcription, which elicits survival signals in HeLa cells. ..
  17. Song B, Xie B, Wang C, Li M. Caspase-3 is a target gene of c-Jun:ATF2 heterodimers during apoptosis induced by activity deprivation in cerebellar granule neurons. Neurosci Lett. 2011;505:76-81 pubmed publisher
    ..that the caspase-3 gene is transactivated and its induction is preceded by c-Jun NH(2)-terminal kinase (JNK)/c-Jun:ATF2 pathway activation following activity deprivation in CGNs...
  18. Pearson A, Curtis M, Waldvogel H, Faull R, Dragunow M. Activating transcription factor 2 expression in the adult human brain: association with both neurodegeneration and neurogenesis. Neuroscience. 2005;133:437-51 pubmed
    Activating transcription factor 2 (ATF2) is a member of the activator protein-1 family of transcription factors, which includes c-Jun and c-Fos...
  19. Keklikoglu N. c-Jun, Fra-2, and ATF-2 immunoreactivity in the jejunal tissues of the healthy rat. Dig Dis Sci. 2008;53:2680-6 pubmed publisher
    ..These findings suggest that each member of AP-1 is expressed differently and that ATF-2 is more active than c-Jun and Fra-2 in physiological conditions in healthy rat jejunum. ..
  20. Nieto Bodelón M, Santpere G, Torrejón Escribano B, Puig B, Ferrer I. Expression of transcription factors c-Fos, c-Jun, CREB-1 and ATF-2, and caspase-3 in relation with abnormal tau deposits in Pick's disease. Acta Neuropathol. 2006;111:341-50 pubmed
    ..The present findings are in line with the previous studies showing tau products cleaved by caspase-3, as recognized by specific tau-cleaved antibodies, in Alzheimer's disease and other tauopathies. ..
  21. Meeker R, Fernandes A. Sustained increases in activating transcription factor-2 and activator protein-2 in the rat supraoptic nucleus during water deprivation. Neuroendocrinology. 2002;76:111-20 pubmed
  22. Hu B, Fux C, Martone M, Zivin J, Ellisman M. Persistent phosphorylation of cyclic AMP responsive element-binding protein and activating transcription factor-2 transcription factors following transient cerebral ischemia in rat brain. Neuroscience. 1999;89:437-52 pubmed
    ..The more modest activation of CREB pathways in CA1 neurons may not be enough to overcome the increased stresses in these neurons, contributing to delayed neuronal death. ..
  23. Yoshimura T, Fujisawa J, Yoshida M. Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain. EMBO J. 1990;9:2537-42 pubmed
    ..These structural features and DNA binding properties suggest that TREB proteins are members of a CREB protein family and that some of them (i.e., TREB7 and TREB36) may be involved in p40tax-mediated trans-activation. ..
  24. Feng A, Yu C, Mao Q, Li N, Li Q, Li J. Berberine hydrochloride attenuates cyclooxygenase-2 expression in rat small intestinal mucosa during acute endotoxemia. Fitoterapia. 2011;82:976-82 pubmed publisher
    ..LPS increased phosphorylation of mucosal p38 MAPK and ATF2 as well as production of ATF2, whereas BBR attenuated these effects...
  25. Lee M, Jung C, Lee K, Choi Y, Hong S, Cheong J. Activating transcription factor-2 mediates transcriptional regulation of gluconeogenic gene PEPCK by retinoic acid. Diabetes. 2002;51:3400-7 pubmed
    ..Taken together, the data suggest that RA activates the p38beta kinase pathway leading to phosphorylation and activation of ATF-2, thereby enhancing PEPCK gene transcription and glucose production. ..
  26. Yamada T, Yoshiyama Y, Kawaguchi N. Expression of activating transcription factor-2 (ATF-2), one of the cyclic AMP response element (CRE) binding proteins, in Alzheimer disease and non-neurological brain tissues. Brain Res. 1997;749:329-34 pubmed
  27. Xiao J, Liang D, Zhang H, Liu Y, Zhang D, Liu Y, et al. MicroRNA-204 is required for differentiation of human-derived cardiomyocyte progenitor cells. J Mol Cell Cardiol. 2012;53:751-9 pubmed publisher
    ..This study indicates that miRNA-204 is among the regulators that drive hCMPC proliferation and differentiation, and miRNA-204 might be used to influence cell fate. ..
  28. Xiao L, Rao J, Zou T, Liu L, Marasa B, Chen J, et al. Polyamines regulate the stability of activating transcription factor-2 mRNA through RNA-binding protein HuR in intestinal epithelial cells. Mol Biol Cell. 2007;18:4579-90 pubmed
    ..These results indicate that polyamines modulate the stability of ATF-2 mRNA by altering cytoplasmic HuR levels and that polyamine-modulated ATF-2 expression plays a critical role in regulating epithelial apoptosis. ..
  29. Pruitt K, Maglott D. RefSeq and LocusLink: NCBI gene-centered resources. Nucleic Acids Res. 2001;29:137-40 pubmed
    ..Additional information about LocusLink and RefSeq is available at ..
  30. Lee H, Sheu S, Yen H, Lai W, Chang J. JNK/ATF2 pathway is involved in iodinated contrast media-induced apoptosis. Am J Nephrol. 2010;31:125-33 pubmed publisher
    Notably, activating transcriptional factor 2 (ATF2), a histone-modification gene, is involved in oxidative stress-induced apoptosis. The aim of this study was to clarify the role of ATF2 in contrast media-induced nephropathy...
  31. Ma C, Ying C, Yuan Z, Song B, Li D, Liu Y, et al. dp5/HRK is a c-Jun target gene and required for apoptosis induced by potassium deprivation in cerebellar granule neurons. J Biol Chem. 2007;282:30901-9 pubmed
    ..Furthermore, a gel shift assay showed that a specific complex containing c-Jun and ATF2 recognized this site and increased in potassium-deprived cerebellar granule neurons...
  32. Shuman J, Cheong J, Coligan J. ATF-2 and C/EBPalpha can form a heterodimeric DNA binding complex in vitro. Functional implications for transcriptional regulation. J Biol Chem. 1997;272:12793-800 pubmed
    ..Moreover, the formation of ATF-2:C/EBPbeta heterodimers suggests that cross-family dimerization with ATF-2 may be a general property for C/EBP family proteins. ..
  33. Ji L, Mochon E, Arcinas M, Boxer L. CREB proteins function as positive regulators of the translocated bcl-2 allele in t(14;18) lymphomas. J Biol Chem. 1996;271:22687-91 pubmed
    ..We conclude that the CRE site functions as a positive regulatory site for the translocated bcl-2 allele in t(14;18) lymphomas. ..
  34. Lin D, Chang I, Tseng A, Wu M, Chen C, Patenaude C, et al. Transforming growth factor beta up-regulates cysteine-rich protein 2 in vascular smooth muscle cells via activating transcription factor 2. J Biol Chem. 2008;283:15003-14 pubmed publisher
    ..Gel mobility shift assays revealed that mainly ATF2 bound to this CRE-like element, and mutation of the CRE sequences abolished binding...
  35. Wang L, Payton R, Dai W, Lu L. Hyperosmotic stress-induced ATF-2 activation through Polo-like kinase 3 in human corneal epithelial cells. J Biol Chem. 2011;286:1951-8 pubmed publisher
  36. Lim J, Park S, Hwang H, Park E, Nam J, Kim J, et al. TGF-beta1 induces cardiac hypertrophic responses via PKC-dependent ATF-2 activation. J Mol Cell Cardiol. 2005;39:627-36 pubmed
    ..Our results suggest that PKC is involved in TGF-beta1-induced cardiac hypertrophic responses in our cell culture system and that ATF-2 activation plays a role. ..
  37. Feng A, Zhou G, Yuan X, Huang X, Zhang Z, Zhang T. Inhibitory effect of baicalin on iNOS and NO expression in intestinal mucosa of rats with acute endotoxemia. PLoS ONE. 2013;8:e80997 pubmed publisher
    ..receptor gamma (PPAR?) content, but also activated p38 and activating transcription factor 2 (ATF2) and inactivated PPAR? via phosphorylation...
  38. Xiao L, Rao J, Zou T, Liu L, Yu T, Zhu X, et al. Induced ATF-2 represses CDK4 transcription through dimerization with JunD inhibiting intestinal epithelial cell growth after polyamine depletion. Am J Physiol Cell Physiol. 2010;298:C1226-34 pubmed publisher
    ..These results indicate that induced ATF-2/JunD association following polyamine depletion represses CDK4 transcription, thus contributing to the inhibition of IEC growth. ..
  39. Fischer T, Ludwig S, Flory E, Gambaryan S, Singh K, Finn P, et al. Activation of cardiac c-Jun NH(2)-terminal kinases and p38-mitogen-activated protein kinases with abrupt changes in hemodynamic load. Hypertension. 2001;37:1222-8 pubmed
    ..Thus, hemodynamic stress of the adult rat heart in vivo results in rapid activation of several parallel MAPK kinase cascades, particularly stress-activated MAPK and p38-MAPK and their target transcription factors c-Jun and ATF-2. ..
  40. Kreutz M, Bien A, Vorwerk C, Bockers T, Seidenbecher C, Tischmeyer W, et al. Co-expression of c-Jun and ATF-2 characterizes the surviving retinal ganglion cells which maintain axonal connections after partial optic nerve injury. Brain Res Mol Brain Res. 1999;69:232-41 pubmed
    ..In disconnected RGCs, however, low levels of ATF-2 and the co-expression of c-Jun may be related to cell death. ..