activating transcription factors


Summary: Activating transcription factors were originally identified as DNA-BINDING PROTEINS that interact with early promoters from ADENOVIRUSES. They are a family of basic leucine zipper transcription factors that bind to the consensus site TGACGTCA of the cyclic AMP response element, and are closely related to CYCLIC AMP-RESPONSIVE DNA-BINDING PROTEIN.

Top Publications

  1. Liu F, Green M. A specific member of the ATF transcription factor family can mediate transcription activation by the adenovirus E1a protein. Cell. 1990;61:1217-24 pubmed
    ..We provide evidence that E1a interacts with a discrete region of promoter-bound ATF-2, thereby positioning the E1a activating region at a viral promoter. ..
  2. Gho J, Ip W, Chan K, Law P, Lai P, Wong N. Re-expression of transcription factor ATF5 in hepatocellular carcinoma induces G2-M arrest. Cancer Res. 2008;68:6743-51 pubmed publisher
    ..In conclusion, our finding supports a tumor suppressive role for ATF5 in HCC, and highlighted ID1 as a potential downstream target. ..
  3. Angelastro J, Canoll P, Kuo J, Weicker M, Costa A, Bruce J, et al. Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. Oncogene. 2006;25:907-16 pubmed
    ..The widespread expression of ATF5 in glioblastomas and the selective effect of interference with ATF5 function/expression on their survival suggest that ATF5 may be an attractive target for therapeutic intervention in such tumors. ..
  4. Hamard P, Dalbies Tran R, Hauss C, Davidson I, Kedinger C, Chatton B. A functional interaction between ATF7 and TAF12 that is modulated by TAF4. Oncogene. 2005;24:3472-83 pubmed
  5. Ciaccio N, Laurence J. Effects of disulfide bond formation and protein helicity on the aggregation of activating transcription factor 5. Mol Pharm. 2009;6:1205-15 pubmed publisher
    ..Moreover, this work has general implications for analyzing stability of helical proteins in vitro as well as the specific atomic-level interactions in ATF5 that contribute to instability and self-association. ..
  6. Kon N, Schroeder S, Krawchuk M, Wahls W. Regulation of the Mts1-Mts2-dependent ade6-M26 meiotic recombination hot spot and developmental decisions by the Spc1 mitogen-activated protein kinase of fission yeast. Mol Cell Biol. 1998;18:7575-83 pubmed
    ..Meiotic recombination hot spot function is likely the result of DNA conformational changes imparted by binding of the Mts1-Mts2 meiotic transcription factor. ..
  7. 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
    ..These results demonstrate that eIF2 kinases direct the translational expression of multiple transcription regulators by a mechanism involving delayed translation reinitiation. ..
  8. Hamard P, Boyer Guittaut M, Camuzeaux B, Dujardin D, Hauss C, OELGESCHLAGER T, et al. Sumoylation delays the ATF7 transcription factor subcellular localization and inhibits its transcriptional activity. Nucleic Acids Res. 2007;35:1134-44 pubmed
    ..Furthermore, SUMO conjugation inhibits ATF7 transactivation activity by (i) impairing its association with TAF12 and (ii) blocking its binding-to-specific sequences within target promoters. ..
  9. Kim H, Choi E, Shin J, Jang Y, Park S. Regulation of Swi6/HP1-dependent heterochromatin assembly by cooperation of components of the mitogen-activated protein kinase pathway and a histone deacetylase Clr6. J Biol Chem. 2004;279:42850-9 pubmed
    ..These findings suggest a role for the mitogen-activated protein kinase pathway and histone deacetylase in Swi6-based heterochromatin assembly. ..

More Information


  1. Jia S, Noma K, Grewal S. RNAi-independent heterochromatin nucleation by the stress-activated ATF/CREB family proteins. Science. 2004;304:1971-6 pubmed
    ..These analyses link ATF/CREB family proteins, involved in cellular response to environmental stresses, to nucleation of constitutive heterochromatin. ..
  2. Persengiev S, Devireddy L, Green M. Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors. Genes Dev. 2002;16:1806-14 pubmed
    ..However, constitutive expression of ATFx renders cells resistant to 24p3-mediated apoptosis. Collectively, our results indicate that ATFx is an anti-apoptotic factor, a novel role for an ATF protein. ..
  3. Watanabe Y, Yamamoto M. Schizosaccharomyces pombe pcr1+ encodes a CREB/ATF protein involved in regulation of gene expression for sexual development. Mol Cell Biol. 1996;16:704-11 pubmed
    ..Alternatively, its activity may be independent of PKA, and full induction of ste11 and fbp1 expression requires the function of Pcr1 in addition to elimination of the repression by PKA. ..
  4. Wei Y, Ge Y, Zhou F, Chen H, Cui C, Liu D, et al. Identification and characterization of the promoter of human ATF5 gene. J Biochem. 2010;148:171-8 pubmed publisher
    ..Thus, our studies not only provided molecular basis of ATF5 transcriptional regulation, but also identified ATF5 as a target gene of EBF1 transcription factor. ..
  5. Gaits F, Degols G, Shiozaki K, Russell P. Phosphorylation and association with the transcription factor Atf1 regulate localization of Spc1/Sty1 stress-activated kinase in fission yeast. Genes Dev. 1998;12:1464-73 pubmed
    ..Nuclear localization of Atf1 requires Pcr1, a heterodimerization partner of Atf1. These studies show that phosphorylation and association with Atf1 are required for nuclear localization of Spc1. ..
  6. Mata J, Lyne R, Burns G, Bahler J. The transcriptional program of meiosis and sporulation in fission yeast. Nat Genet. 2002;32:143-7 pubmed
  7. Camuzeaux B, Diring J, Hamard P, Oulad Abdelghani M, Donzeau M, Vigneron M, et al. p38beta2-mediated phosphorylation and sumoylation of ATF7 are mutually exclusive. J Mol Biol. 2008;384:980-91 pubmed publisher
    ..Our data therefore conclusively establish that sumoylation and phosphorylation of ATF7 are two antagonistic posttranslational modifications. ..
  8. Kon N, Krawchuk M, Warren B, Smith G, Wahls W. Transcription factor Mts1/Mts2 (Atf1/Pcr1, Gad7/Pcr1) activates the M26 meiotic recombination hotspot in Schizosaccharomyces pombe. Proc Natl Acad Sci U S A. 1997;94:13765-70 pubmed
    ..pombe genome, suggesting that these factors help regulate the timing and distribution of homologous recombination. ..
  9. Garcia Gimeno M, Struhl K. Aca1 and Aca2, ATF/CREB activators in Saccharomyces cerevisiae, are important for carbon source utilization but not the response to stress. Mol Cell Biol. 2000;20:4340-9 pubmed
    ..In addition, Acr1 does not affect a number of phenotypes that arise from loss of Aca2. Thus, members of the S. cerevisiae ATF/CREB family have overlapping, but distinct, biological functions and target genes. ..
  10. Ciaccio N, Moreno M, Bauer R, Laurence J. High-yield expression in E. coli and refolding of the bZIP domain of activating transcription factor 5. Protein Expr Purif. 2008;62:235-43 pubmed publisher
    ..Polyacrylamide gel electrophoresis and mass spectrometry were used to confirm that ATF5 can participate in homodimer formation and that this dimerization is mediated by disulfide bond formation. ..
  11. Al Sarraj J, Vinson C, Thiel G. Regulation of asparagine synthetase gene transcription by the basic region leucine zipper transcription factors ATF5 and CHOP. Biol Chem. 2005;386:873-9 pubmed
    ..These data indicate that CHOP functions as a shut-off-device for nutrient deprivation-induced gene transcription. ..
  12. Forgacs E, Gupta S, Kerry J, Semmes O. The bZIP transcription factor ATFx binds human T-cell leukemia virus type 1 (HTLV-1) Tax and represses HTLV-1 long terminal repeat-mediated transcription. J Virol. 2005;79:6932-9 pubmed
    ..We propose that recruitment of ATFx to the HTLV-1 LTR serves to link viral transcription with critical events in cellular homeostasis. ..
  13. Kilberg M, Balasubramanian M, Fu L, Shan J. The transcription factor network associated with the amino acid response in mammalian cells. Adv Nutr. 2012;3:295-306 pubmed publisher
  14. Eshaghi M, Lee J, Zhu L, Poon S, Li J, Cho K, et al. Genomic binding profiling of the fission yeast stress-activated MAPK Sty1 and the bZIP transcriptional activator Atf1 in response to H2O2. PLoS ONE. 2010;5:e11620 pubmed publisher
  15. Li G, Li W, Angelastro J, Greene L, Liu D. Identification of a novel DNA binding site and a transcriptional target for activating transcription factor 5 in c6 glioma and mcf-7 breast cancer cells. Mol Cancer Res. 2009;7:933-43 pubmed publisher
    ..These data provide new insight on the mechanisms by which ATF5 promotes gene regulation and cancer-specific cell survival. ..
  16. Sakamoto K, Iwashita K, Yamada O, Kobayashi K, Mizuno A, Akita O, et al. Aspergillus oryzae atfA controls conidial germination and stress tolerance. Fungal Genet Biol. 2009;46:887-97 pubmed publisher
    ..We therefore concluded that atfA is involved in germination via carbon and nitrogen source metabolism. ..
  17. Bocco J, Bahr A, Goetz J, Hauss C, Kallunki T, Kedinger C, et al. In vivo association of ATFa with JNK/SAP kinase activities. Oncogene. 1996;12:1971-80 pubmed
    ..Taken together, these observations suggest that the ATFa proteins, among other CREB/ATF proteins, may be important effectors of cell signalling pathways. ..
  18. Greene L, Lee H, Angelastro J. The transcription factor ATF5: role in neurodevelopment and neural tumors. J Neurochem. 2009;108:11-22 pubmed publisher
    ..Further studies are needed to identify the transcriptional targets of ATF5 and the mechanisms by which its expression is regulated in neuroprogenitors and tumors. ..
  19. Shivers R, Pagano D, Kooistra T, Richardson C, Reddy K, Whitney J, et al. Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans. PLoS Genet. 2010;6:e1000892 pubmed publisher
  20. Hansen M, Mitchelmore C, Kjaerulff K, Rasmussen T, Pedersen K, Jensen N. Mouse Atf5: molecular cloning of two novel mRNAs, genomic organization, and odorant sensory neuron localization. Genomics. 2002;80:344-50 pubmed
    ..This suggests a role for ATF5 in odorant sensory neuron differentiation. ..
  21. Rep M, Proft M, Remize F, Tamas M, Serrano R, Thevelein J, et al. The Saccharomyces cerevisiae Sko1p transcription factor mediates HOG pathway-dependent osmotic regulation of a set of genes encoding enzymes implicated in protection from oxidative damage. Mol Microbiol. 2001;40:1067-83 pubmed
    ..The five Sko1p target genes described here are suitable models for studying the interplay between osmotic and oxidative responses at the molecular and physiological levels. ..
  22. Wahls W, Smith G. A heteromeric protein that binds to a meiotic homologous recombination hot spot: correlation of binding and hot spot activity. Genes Dev. 1994;8:1693-702 pubmed
    ..These and other data suggest that homologous recombination may be regulated primarily by discrete DNA sites and proteins that interact with those sites. ..
  23. Wang H, Lin G, Zhang Z. ATF5 promotes cell survival through transcriptional activation of Hsp27 in H9c2 cells. Cell Biol Int. 2007;31:1309-15 pubmed
    ..Taken together, our results indicated that ATF5 promoted H9c2 cell survival in heat shock stress at least through activation of Hsp27. ..
  24. Liu X, Liu D, Qian D, Dai J, An Y, Jiang S, et al. Nucleophosmin (NPM1/B23) interacts with activating transcription factor 5 (ATF5) protein and promotes proteasome- and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells. J Biol Chem. 2012;287:19599-609 pubmed publisher
    ..Our study establishes a mechanistic link between elevated NPM1 expression and depressed ATF5 in HCC and suggests that regulation of ATF5 by NPM1 plays an important role in the proliferation and survival of HCC. ..
  25. Dluzen D, Li G, Tacelosky D, Moreau M, Liu D. BCL-2 is a downstream target of ATF5 that mediates the prosurvival function of ATF5 in a cell type-dependent manner. J Biol Chem. 2011;286:7705-13 pubmed publisher
  26. Kim S, Wagner S, Liu F, O Reilly M, Robbins P, Green M. Retinoblastoma gene product activates expression of the human TGF-beta 2 gene through transcription factor ATF-2. Nature. 1992;358:331-4 pubmed
    ..Third, ATF-2 in nuclear extracts can interact with pRb. Our results reveal a new mechanism by which pRb constrains cellular proliferation: by activating expression of the inhibitory growth factor, TGF-beta 2. ..
  27. Sansó M, Gogol M, Ayte J, Seidel C, Hidalgo E. Transcription factors Pcr1 and Atf1 have distinct roles in stress- and Sty1-dependent gene regulation. Eukaryot Cell. 2008;7:826-35 pubmed publisher
    ..Furthermore, these analyses show that both proteins have a global repressive effect on stress-dependent and stress-independent genes. ..
  28. Pascual M, Gomez Lechon M, Castell J, Jover R. ATF5 is a highly abundant liver-enriched transcription factor that cooperates with constitutive androstane receptor in the transactivation of CYP2B6: implications in hepatic stress responses. Drug Metab Dispos. 2008;36:1063-72 pubmed publisher
    ..Moreover, ATF5 and its target gene CYP2B6 are induced under different stress conditions, suggesting a new potential mechanism to adapt hepatic cytochrome P450 expression to diverse endobiotic/xenobiotic harmful stress. ..
  29. Rivera Cancel G, Motta Mena L, Gardner K. Identification of natural and artificial DNA substrates for light-activated LOV-HTH transcription factor EL222. Biochemistry. 2012;51:10024-34 pubmed publisher
    ..Taken together, these results shed light on the native function of EL222 and provide useful reagents for further basic and applications research of this versatile protein. ..
  30. Watatani Y, Ichikawa K, Nakanishi N, Fujimoto M, Takeda H, Kimura N, et al. Stress-induced translation of ATF5 mRNA is regulated by the 5'-untranslated region. J Biol Chem. 2008;283:2543-53 pubmed
    ..These results suggest that translation of ATF5 is regulated by the alternative 5'-UTR region of its mRNA, and ATF5 may play a role in protecting cells from amino acid limitation or arsenite-induced oxidative stress. ..
  31. Shiozaki K, Russell P. Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast. Genes Dev. 1996;10:2276-88 pubmed
    ..However, unlike spc1- mutants, atf1- cells have no mitotic cell-cycle defect, indicating that the stress response pathway bifurcates at Spc1 to regulate independently meiosis and mitosis. ..
  32. Goetz J, Chatton B, Mattei M, Kedinger C. Structure and expression of the ATFa gene. J Biol Chem. 1996;271:29589-98 pubmed
    ..The possible significance of coexpression of ATFa, ATF-2, and Jun at similar sites in the brain is discussed. ..
  33. Steiner W, Schreckhise R, Smith G. Meiotic DNA breaks at the S. pombe recombination hot spot M26. Mol Cell. 2002;9:847-55 pubmed
    ..Break frequency is strongly correlated with recombination frequency for these alleles. The occurrence of breaks at M26 suggests mechanistic similarities to hot spots in the distantly related yeast Saccharomyces cerevisiae. ..
  34. Persengiev S, Green M. The role of ATF/CREB family members in cell growth, survival and apoptosis. Apoptosis. 2003;8:225-8 pubmed
    ..A better understanding of ATFx function should provide new insight into the processes that control apoptotic cascades. ..
  35. Yamada T, Mizuno K, Hirota K, Kon N, Wahls W, Hartsuiker E, et al. Roles of histone acetylation and chromatin remodeling factor in a meiotic recombination hotspot. EMBO J. 2004;23:1792-803 pubmed
    ..These results suggest that HATs and ADCRs cooperatively alter local chromatin structure, as in selective transcription activation, to activate meiotic recombination at M26 in a site-specific manner. ..
  36. Angelastro J, Mason J, Ignatova T, Kukekov V, Stengren G, Goldman J, et al. Downregulation of activating transcription factor 5 is required for differentiation of neural progenitor cells into astrocytes. J Neurosci. 2005;25:3889-99 pubmed
    ..These findings identify ATF5 as a key regulator of astrocyte formation and potentially of the VZ to SVZ transition. ..
  37. Schrot R, Ma J, Greco C, ARIAS A, Angelastro J. Organotypic distribution of stem cell markers in formalin-fixed brain harboring glioblastoma multiforme. J Neurooncol. 2007;85:149-57 pubmed
  38. Sánchez Tilló E, Liu Y, de Barrios O, Siles L, Fanlo L, Cuatrecasas M, et al. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci. 2012;69:3429-56 pubmed publisher
    ..Upregulated expression of these EMT-activating transcription factors (EMT-ATFs) promotes tumor invasiveness in cell lines and xenograft mice models and has been ..
  39. Steiner W, Smith G. Natural meiotic recombination hot spots in the Schizosaccharomyces pombe genome successfully predicted from the simple sequence motif M26. Mol Cell Biol. 2005;25:9054-62 pubmed
    ..M26 may be the first example among a diverse group of simple sequences that determine the distribution, and hence predictability, of meiotic recombination hot spots in eukaryotic genomes. ..
  40. Angelastro J, Ignatova T, Kukekov V, Steindler D, Stengren G, Mendelsohn C, et al. Regulated expression of ATF5 is required for the progression of neural progenitor cells to neurons. J Neurosci. 2003;23:4590-600 pubmed
    ..These findings indicate that ATF5 blocks the differentiation of neuroprogenitor cells into neurons and must be downregulated to permit this process to occur. ..
  41. Wei Y, Jiang J, Liu D, Zhou J, Chen X, Zhang S, et al. Cdc34-mediated degradation of ATF5 is blocked by cisplatin. J Biol Chem. 2008;283:18773-81 pubmed publisher
    ..In summary, a down-regulation of proteasome-mediated degradation of ATF5 might contribute to cisplatin-induced apoptosis, providing a new mechanism of cisplatin-induced apoptosis. ..
  42. Maekawa T, Kim S, Nakai D, Makino C, Takagi T, Ogura H, et al. Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene. EMBO J. 2010;29:196-208 pubmed publisher
    ..Thus, ATF-7 may have a critical role in gene expression induced by social isolation stress. ..
  43. Balázs A, Pocsi I, Hamari Z, Leiter E, Emri T, Miskei M, et al. AtfA bZIP-type transcription factor regulates oxidative and osmotic stress responses in Aspergillus nidulans. Mol Genet Genomics. 2010;283:289-303 pubmed publisher
  44. Reiter W, Watt S, Dawson K, Lawrence C, Bahler J, Jones N, et al. Fission yeast MAP kinase Sty1 is recruited to stress-induced genes. J Biol Chem. 2008;283:9945-56 pubmed publisher
    ..Consistent with this delay, Sty1 and Atf1 cannot be detected at these promoters in this condition, suggesting that their association with chromatin is weak or transient in the absence of Pcr1. ..
  45. Gao J, Davidson M, Wahls W. Distinct regions of ATF/CREB proteins Atf1 and Pcr1 control recombination hotspot ade6-M26 and the osmotic stress response. Nucleic Acids Res. 2008;36:2838-51 pubmed publisher
    ..These findings reveal the functional organization of Atf1 and Pcr1, and illustrate several mechanisms by which bZIP proteins can regulate multiple, seemingly disparate activities...
  46. Sheng Z, Li L, Zhu L, Smith T, Demers A, Ross A, et al. A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications. Nat Med. 2010;16:671-7 pubmed publisher
    ..Our results demonstrate that ATF5 is essential in malignant glioma genesis and reveal that the ATF5-mediated survival pathway described here provides potential therapeutic targets for treatment of malignant glioma. ..
  47. Bahr A, De Graeve F, Kedinger C, Chatton B. Point mutations causing Bloom's syndrome abolish ATPase and DNA helicase activities of the BLM protein. Oncogene. 1998;17:2565-71 pubmed
    ..These results provide the first evidence suggesting that the enzymatic activities of the BLM product are implicated in the upholding of genomic integrity. ..
  48. Borden K. Two mutant binding sites of the activating transcription factor region within the E2A promoter of adenovirus exist in a novel conformation. Biochim Biophys Acta. 1994;1219:505-14 pubmed
    ..Both factors are important to the protein nucleic acid recognition process and thus to cellular control of transcription. ..
  49. Slice L, Han S, Simon M. Galphaq signaling is required for Rho-dependent transcriptional activation of the cyclooxygenase-2 promoter in fibroblasts. J Cell Physiol. 2003;194:127-38 pubmed
    ..These results demonstrate that calcium signaling mediated by Galpha(q) and Rho play critical roles in GRP-dependent COX-2 expression in fibroblasts. ..
  50. Peters C, Liang X, Li S, Kannan S, Peng Y, Taub R, et al. ATF-7, a novel bZIP protein, interacts with the PRL-1 protein-tyrosine phosphatase. J Biol Chem. 2001;276:13718-26 pubmed
  51. Tajima S, Aida Y. Induction of expression of bovine leukemia virus (BLV) in blood taken from BLV-infected cows without removal of plasma. Microbes Infect. 2005;7:1211-6 pubmed
    ..Our data suggest that the actual collection of blood and pathways that involve PKC and Ca2+ might play important roles in the reactivation of expression of BLV in blood from infected cattle...
  52. Nishioka T, Miyai Y, Haga H, Kawabata K, Shirato H, Homma A, et al. Novel function of transcription factor ATF5: blockade of p53-dependent apoptosis induced by ionizing irradiation. Cell Struct Funct. 2009;34:17-22 pubmed
    ..It seems likely that ATF5 is a potent repressor of p53 and elevated expression of ATF5 in a tumor may relate to enhanced malignant phenotypes, such as radioresistance or greater cell motility. ..
  53. Dryer R, Covey L. A novel NF-kappa B-regulated site within the human I gamma 1 promoter requires p300 for optimal transcriptional activity. J Immunol. 2005;175:4499-507 pubmed
    ..Together these data support a model whereby CREB and multiple NF-kappaB complexes bind to the Igamma1 promoter and recruit p300. CD40 signals induce p300-dependent changes that result in optimal Igamma1 promoter activity. ..