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Gene Review

ATF1  -  activating transcription factor 1

Homo sapiens

Synonyms: EWS-ATF1, FUS/ATF-1, TREB36
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Disease relevance of ATF1


High impact information on ATF1

  • The deduced chimaeric protein encoded by the der(22) chromosome consists of the N-terminal domain of EWS linked to the bZIP domain of ATF-1, a transcription factor which may normally be regulated by cAMP [6].
  • These studies show that phosphorylation and association with Atf1 are required for nuclear localization of Spc1 [7].
  • This control is partly mediated through Atf1, a transcription factor homologous to human ATF2 [8].
  • How Spc1 controls Atf1, and how the cells tailor gene expression patterns to different forms of stress, are unknown [8].
  • Csx1 associates with and stabilizes atf1+ mRNA in response to oxidative stress [8].

Chemical compound and disease context of ATF1


Biological context of ATF1


Anatomical context of ATF1


Associations of ATF1 with chemical compounds


Physical interactions of ATF1


Regulatory relationships of ATF1


Other interactions of ATF1

  • 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 [30].
  • A large family of mammalian transcription factors including multiple variants of CREB, CREM and ATF1 have been implicated in signal transduction by cAMP and other cellular pathways [31].
  • The AFH, however, did not express the MITF-M transcript, supporting the theory that MITF-M expression in CCS is a reflection of its cellular origin, rather than a consequence of the presence of an EWSR1-ATF1 fusion protein [3].
  • TREB7 and TREB36 protected all three repeats of the 21 bp, but TREB5 protected only the second repeat [30].
  • Furthermore, transient cotransfections of a CIITA-PIII luciferase reporter construct with either CREB-1 or ATF-1 boost CIITA-PIII trans-activation in a dose-dependent manner, which was further enhanced by addition of general coactivator CREB-binding protein [32].

Analytical, diagnostic and therapeutic context of ATF1


  1. A novel zinc finger gene is fused to EWS in small round cell tumor. Mastrangelo, T., Modena, P., Tornielli, S., Bullrich, F., Testi, M.A., Mezzelani, A., Radice, P., Azzarelli, A., Pilotti, S., Croce, C.M., Pierotti, M.A., Sozzi, G. Oncogene (2000) [Pubmed]
  2. MMSP tumor cells expressing the EWS/ATF1 oncogene do not support cAMP-inducible transcription. Li, K.K., Lee, K.A. Oncogene (1998) [Pubmed]
  3. Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma. Hallor, K.H., Mertens, F., Jin, Y., Meis-Kindblom, J.M., Kindblom, L.G., Behrendtz, M., Kalén, A., Mandahl, N., Panagopoulos, I. Genes Chromosomes Cancer (2005) [Pubmed]
  4. Association of the t(12;22)(q13;q12) EWS/ATF1 rearrangement with polyphenotypic round cell sarcoma of bone: a case report. Somers, G.R., Viero, S., Nathan, P.C., Teshima, I., Pereira, C., Zielenska, M. Am. J. Surg. Pathol. (2005) [Pubmed]
  5. Tumor cell viability in clear cell sarcoma requires DNA binding activity of the EWS/ATF1 fusion protein. Bosilevac, J.M., Olsen, R.J., Bridge, J.A., Hinrichs, S.H. J. Biol. Chem. (1999) [Pubmed]
  6. EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Zucman, J., Delattre, O., Desmaze, C., Epstein, A.L., Stenman, G., Speleman, F., Fletchers, C.D., Aurias, A., Thomas, G. Nat. Genet. (1993) [Pubmed]
  7. Phosphorylation and association with the transcription factor Atf1 regulate localization of Spc1/Sty1 stress-activated kinase in fission yeast. Gaits, F., Degols, G., Shiozaki, K., Russell, P. Genes Dev. (1998) [Pubmed]
  8. RNA-binding protein Csx1 mediates global control of gene expression in response to oxidative stress. Rodríguez-Gabriel, M.A., Burns, G., McDonald, W.H., Martín, V., Yates, J.R., Bähler, J., Russell, P. EMBO J. (2003) [Pubmed]
  9. Expression profiling of t(12;22) positive clear cell sarcoma of soft tissue cell lines reveals characteristic up-regulation of potential new marker genes including ERBB3. Schaefer, K.L., Brachwitz, K., Wai, D.H., Braun, Y., Diallo, R., Korsching, E., Eisenacher, M., Voss, R., Van Valen, F., Baer, C., Selle, B., Spahn, L., Liao, S.K., Lee, K.A., Hogendoorn, P.C., Reifenberger, G., Gabbert, H.E., Poremba, C. Cancer Res. (2004) [Pubmed]
  10. A repetitive element containing a critical tyrosine residue is required for transcriptional activation by the EWS/ATF1 oncogene. Feng, L., Lee, K.A. Oncogene (2001) [Pubmed]
  11. Role of tissue-specific transcription factor LFB3 in a cyclic AMP-responsive enhancer of the urokinase-type plasminogen activator gene in LLC-PK1 cells. Soubt, M.K., Marksitzer, R., Menoud, P.A., Nagamine, Y. Mol. Cell. Biol. (1998) [Pubmed]
  12. Calmodulin-dependent protein kinase II potentiates transcriptional activation through activating transcription factor 1 but not cAMP response element-binding protein. Shimomura, A., Ogawa, Y., Kitani, T., Fujisawa, H., Hagiwara, M. J. Biol. Chem. (1996) [Pubmed]
  13. Inhibition of activating transcription factor 1- and cAMP-responsive element-binding protein-activated transcription by an intracellular single chain Fv fragment. Bosilevac, J.M., Gilchrist, C.A., Jankowski, P.E., Paul, S., Rees, A.R., Hinrichs, S.H. J. Biol. Chem. (1998) [Pubmed]
  14. BRCA1 physically and functionally interacts with ATF1. Houvras, Y., Benezra, M., Zhang, H., Manfredi, J.J., Weber, B.L., Licht, J.D. J. Biol. Chem. (2000) [Pubmed]
  15. Epidermal growth factor induction of the c-jun promoter by a Rac pathway. Clarke, N., Arenzana, N., Hai, T., Minden, A., Prywes, R. Mol. Cell. Biol. (1998) [Pubmed]
  16. Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses. Panagopoulos, I., Mertens, F., Dêbiec-Rychter, M., Isaksson, M., Limon, J., Kardas, I., Domanski, H.A., Sciot, R., Perek, D., Crnalic, S., Larsson, O., Mandahl, N. Int. J. Cancer (2002) [Pubmed]
  17. ATF1 and CREB trans-activate a cell cycle regulated histone H4 gene at a distal nuclear matrix associated promoter element. Guo, B., Stein, J.L., van Wijnen, A.J., Stein, G.S. Biochemistry (1997) [Pubmed]
  18. The activity of the Epstein-Barr virus BamHI W promoter in B cells is dependent on the binding of CREB/ATF factors. Kirby, H., Rickinson, A., Bell, A. J. Gen. Virol. (2000) [Pubmed]
  19. The melanocyte inducing factor MITF is stably expressed in cell lines from human clear cell sarcoma. Li, K.K., Goodall, J., Goding, C.R., Liao, S.K., Wang, C.H., Lin, Y.C., Hiraga, H., Nojima, T., Nagashima, K., Schaefer, K.L., Lee, K.A. Br. J. Cancer (2003) [Pubmed]
  20. Association of activating transcription factor 2 (ATF2) with the ubiquitin-conjugating enzyme hUBC9. Implication of the ubiquitin/proteasome pathway in regulation of ATF2 in T cells. Firestein, R., Feuerstein, N. J. Biol. Chem. (1998) [Pubmed]
  21. ATF1 phosphorylation by the ERK MAPK pathway is required for epidermal growth factor-induced c-jun expression. Gupta, P., Prywes, R. J. Biol. Chem. (2002) [Pubmed]
  22. Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M transcripts and histopathological and ultrastructural analysis of 12 cases. Antonescu, C.R., Tschernyavsky, S.J., Woodruff, J.M., Jungbluth, A.A., Brennan, M.F., Ladanyi, M. The Journal of molecular diagnostics : JMD. (2002) [Pubmed]
  23. Activating transcription factor-1 is a specific antagonist of the cyclic adenosine 3'.5'-monophosphate (cAMP) response element-binding protein-1-mediated response to cAMP. Ellis, M.J., Lindon, A.C., Flint, K.J., Jones, N.C., Goodbourn, S. Mol. Endocrinol. (1995) [Pubmed]
  24. The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator. Fujimura, Y., Ohno, T., Siddique, H., Lee, L., Rao, V.N., Reddy, E.S. Oncogene (1996) [Pubmed]
  25. Copurification of casein kinase II with transcription factor ATF/E4TF3. Wada, T., Takagi, T., Yamaguchi, Y., Kawase, H., Hiramoto, M., Ferdous, A., Takayama, M., Lee, K.A., Hurst, H.C., Handa, H. Nucleic Acids Res. (1996) [Pubmed]
  26. Ketoconazole suppresses prostaglandin E(2)-induced cyclooxygenase-2 expression in human epidermoid carcinoma A-431 cells. Kanda, N., Watanabe, S. J. Invest. Dermatol. (2002) [Pubmed]
  27. Regulation of activating transcription factor-1 and the cAMP response element-binding protein by Ca2+/calmodulin-dependent protein kinases type I, II, and IV. Sun, P., Lou, L., Maurer, R.A. J. Biol. Chem. (1996) [Pubmed]
  28. Activating transcription factor 1 and cyclic AMP response element modulator can modulate the activity of the immunoglobulin kappa 3' enhancer. Pongubala, J.M., Atchison, M.L. J. Biol. Chem. (1995) [Pubmed]
  29. Activating-transcription-factor (ATF) regulates human 7S L RNA transcription by RNA polymerase III in vivo and in vitro. Bredow, S., Sürig, D., Müller, J., Kleinert, H., Benecke, B.J. Nucleic Acids Res. (1990) [Pubmed]
  30. 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. Yoshimura, T., Fujisawa, J., Yoshida, M. EMBO J. (1990) [Pubmed]
  31. In vitro phosphorylation studies of a conserved region of the transcription factor ATF1. Masson, N., John, J., Lee, K.A. Nucleic Acids Res. (1993) [Pubmed]
  32. Transcriptional regulation of the MHC class II trans-activator (CIITA) promoter III: identification of a novel regulatory region in the 5'-untranslated region and an important role for cAMP-responsive element binding protein 1 and activating transcription factor-1 in CIITA-promoter III transcriptional activation in B lymphocytes. van der Stoep, N., Quinten, E., van den Elsen, P.J. J. Immunol. (2002) [Pubmed]
  33. Loss of expression of the ubiquitous transcription factor cAMP response element-binding protein (CREB) and compensatory overexpression of the activator CREMtau in the human adrenocortical cancer cell line H295R. Groussin, L., Massias, J.F., Bertagna, X., Bertherat, J. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  34. EWS-ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma. Covinsky, M., Gong, S., Rajaram, V., Perry, A., Pfeifer, J. Hum. Pathol. (2005) [Pubmed]
  35. Cytogenetic comparison between clear cell sarcoma and a case of acral clear cell melanoma. Zelger, B.G., Debiec-Rychter, M., Sciot, R., Zelger, B. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. (2003) [Pubmed]
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