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Gene Review

ATF3  -  activating transcription factor 3

Homo sapiens

Synonyms: Activating transcription factor 3, Cyclic AMP-dependent transcription factor ATF-3, cAMP-dependent transcription factor ATF-3
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Disease relevance of ATF3


High impact information on ATF3

  • Opposite responses of Id1 to TGFbeta and the related factor BMP are dictated by the specific ability of the TGFbeta mediator, Smad3, to activate expression of stress response factor ATF3 and then recruit this factor to the Id1 promoter [6].
  • A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells [6].
  • Thus, ATF3 is a novel stress-activated regulator of p53 protein stability/function providing the cell with a means of responding to a wide range of environmental insult, thus maintaining DNA integrity and protecting against cell transformation [7].
  • Activating transcription factor 3 (ATF3) is rapidly induced by diverse environmental insults including genotoxic stress [7].
  • In H2O2-stimulated NP31 cells as well as endothelial cells of glomerulus and aorta of Otsuka-Long-Evans-Tokushima-Fatty diabetic model rats, concomitantly enhanced expressions of ATF3, PAI-1, and p8 were observed [8].

Chemical compound and disease context of ATF3


Biological context of ATF3


Anatomical context of ATF3


Associations of ATF3 with chemical compounds

  • We showed that anisomycin at a low concentration activates the ATF3 promoter and stabilizes the ATF3 mRNA [17].
  • Analysis of ATF3 mRNA turnover revealed that the half-life was increased from about 1 h in control cells to greater than 8 h in the histidine-deprived state, demonstrating mRNA stabilization in response to nutrient deprivation [3].
  • Both amino acid limitation and activation of the endoplasmic reticulum stress response by glucose deprivation caused an increase in ATF3 mRNA content [18].
  • ATF3 protected these cells from tumor necrosis factor (TNF)-alpha-induced apoptosis, as measured by flow cytometric analysis, trypan blue exclusion assay, and cleavage of procaspase 3 and poly(ADP-ribose) polymerase [4].
  • A possible mechanism implicating the C-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) stress-inducible signaling pathway in the induction of the ATF3 gene is discussed [17].

Physical interactions of ATF3

  • EGR-1 binds to the ATF3 promoter as assessed by gel shift assay [1].
  • Immunoprecipitation of HuR-RNA complexes followed by reverse transcriptase-PCR analysis showed that HuR interacted with ATF3 mRNA in vivo and that this interaction increased following amino acid limitation [3].
  • We recently reported that ATF3 interacts with the tumor suppressor p53 to increase its stability in the genotoxic response [19].
  • The ability of ATF3 to stabilize p53-induced pathways thus represents a means of effectively countering DNA damage caused by environmental insult the latter leading to oncogene activation and ultimately malignant transformation [19].
  • 1. LPS stimulation leads to an induction of ATF-3 and JunD factor binding to the CRE/AP-1 site [20].

Regulatory relationships of ATF3


Other interactions of ATF3

  • Collectively, the results provide evidence for a potential role of multiple predicted ATF3 isoforms in the transcriptional regulation of the ASNS gene in response to nutrient deprivation [18].
  • Assignment of UCK2, ATF3 and RGS18 from human chromosome 1 to porcine chromosomes 4, 9 and 10 with somatic and radiation hybrid panels [23].
  • ATF3 and EGR-1 may provide a novel explanation for the antitumorigenic properties of LY294002 in human colorectal cancer cells [1].
  • Progressive deletions of the MMP-2 promoter indicated a 38-base pair region (-1659/-1622) necessary for the ATF3-mediated repression [2].
  • Interaction of RNA-binding proteins HuR and AUF1 with the human ATF3 mRNA 3'-untranslated region regulates its amino acid limitation-induced stabilization [3].

Analytical, diagnostic and therapeutic context of ATF3


  1. Activating transcription factor 3 and early growth response 1 are the novel targets of LY294002 in a phosphatidylinositol 3-kinase-independent pathway. Yamaguchi, K., Lee, S.H., Kim, J.S., Wimalasena, J., Kitajima, S., Baek, S.J. Cancer Res. (2006) [Pubmed]
  2. ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter. Yan, C., Wang, H., Boyd, D.D. J. Biol. Chem. (2002) [Pubmed]
  3. Interaction of RNA-binding proteins HuR and AUF1 with the human ATF3 mRNA 3'-untranslated region regulates its amino acid limitation-induced stabilization. Pan, Y.X., Chen, H., Kilberg, M.S. J. Biol. Chem. (2005) [Pubmed]
  4. Transcriptional repressor activating transcription factor 3 protects human umbilical vein endothelial cells from tumor necrosis factor-alpha-induced apoptosis through down-regulation of p53 transcription. Kawauchi, J., Zhang, C., Nobori, K., Hashimoto, Y., Adachi, M.T., Noda, A., Sunamori, M., Kitajima, S. J. Biol. Chem. (2002) [Pubmed]
  5. Nonrandom chromosomal imbalances in esophageal squamous cell carcinoma cell lines: possible involvement of the ATF3 and CENPF genes in the 1q32 amplicon. Pimkhaokham, A., Shimada, Y., Fukuda, Y., Kurihara, N., Imoto, I., Yang, Z.Q., Imamura, M., Nakamura, Y., Amagasa, T., Inazawa, J. Jpn. J. Cancer Res. (2000) [Pubmed]
  6. A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells. Kang, Y., Chen, C.R., Massagué, J. Mol. Cell (2003) [Pubmed]
  7. Activating transcription factor 3, a stress sensor, activates p53 by blocking its ubiquitination. Yan, C., Lu, D., Hai, T., Boyd, D.D. EMBO J. (2005) [Pubmed]
  8. Oxidative stress-responsive transcription factor ATF3 potentially mediates diabetic angiopathy. Okamoto, A., Iwamoto, Y., Maru, Y. Mol. Cell. Biol. (2006) [Pubmed]
  9. Transcriptional regulation of activating transcription factor 3 involves the early growth response-1 gene. Bottone, F.G., Moon, Y., Alston-Mills, B., Eling, T.E. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  10. Induction of activating transcription factor 3 by anoxia is independent of p53 and the hypoxic HIF signalling pathway. Ameri, K., Hammond, E.M., Culmsee, C., Raida, M., Katschinski, D.M., Wenger, R.H., Wagner, E., Davis, R.J., Hai, T., Denko, N., Harris, A.L. Oncogene (2007) [Pubmed]
  11. Activating transcription factor 3 is up-regulated in patients with hypospadias. Liu, B., Wang, Z., Lin, G., Agras, K., Ebbers, M., Willingham, E., Baskin, L.S. Pediatr. Res. (2005) [Pubmed]
  12. The anti-invasive activity of cyclooxygenase inhibitors is regulated by the transcription factor ATF3 (activating transcription factor 3). Bottone, F.G., Moon, Y., Kim, J.S., Alston-Mills, B., Ishibashi, M., Eling, T.E. Mol. Cancer Ther. (2005) [Pubmed]
  13. The expression of transcription factor activating transcription factor 3 in the human prostate and its regulation by androgen in prostate cancer. Pelzer, A.E., Bektic, J., Haag, P., Berger, A.P., Pycha, A., Schäfer, G., Rogatsch, H., Horninger, W., Bartsch, G., Klocker, H. J. Urol. (2006) [Pubmed]
  14. ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: a novel cardioprotective role of ATF3. Nobori, K., Ito, H., Tamamori-Adachi, M., Adachi, S., Ono, Y., Kawauchi, J., Kitajima, S., Marumo, F., Isobe, M. J. Mol. Cell. Cardiol. (2002) [Pubmed]
  15. Sensory neurons and their supporting cells located in the trigeminal, thoracic and lumbar ganglia differentially express markers of injury following intravenous administration of paclitaxel in the rat. Jimenez-Andrade, J.M., Peters, C.M., Mejia, N.A., Ghilardi, J.R., Kuskowski, M.A., Mantyh, P.W. Neurosci. Lett. (2006) [Pubmed]
  16. ATF3 enhances c-Jun-mediated neurite sprouting. Pearson, A.G., Gray, C.W., Pearson, J.F., Greenwood, J.M., During, M.J., Dragunow, M. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  17. ATF3 gene. Genomic organization, promoter, and regulation. Liang, G., Wolfgang, C.D., Chen, B.P., Chen, T.H., Hai, T. J. Biol. Chem. (1996) [Pubmed]
  18. Amino acid deprivation and endoplasmic reticulum stress induce expression of multiple activating transcription factor-3 mRNA species that, when overexpressed in HepG2 cells, modulate transcription by the human asparagine synthetase promoter. Pan, Y., Chen, H., Siu, F., Kilberg, M.S. J. Biol. Chem. (2003) [Pubmed]
  19. ATF3 regulates the stability of p53: a link to cancer. Yan, C., Boyd, D.D. Cell Cycle (2006) [Pubmed]
  20. ATF and Jun transcription factors, acting through an Ets/CRE promoter module, mediate lipopolysaccharide inducibility of the chemokine RANTES in monocytic Mono Mac 6 cells. Boehlk, S., Fessele, S., Mojaat, A., Miyamoto, N.G., Werner, T., Nelson, E.L., Schlöndorff, D., Nelson, P.J. Eur. J. Immunol. (2000) [Pubmed]
  21. Indole-3-carbinol and 3,3'-diindolylmethane induce expression of NAG-1 in a p53-independent manner. Lee, S.H., Kim, J.S., Yamaguchi, K., Eling, T.E., Baek, S.J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  22. Interleukin-10 induced activating transcription factor 3 transcriptional suppression of matrix metalloproteinase-2 gene expression in human prostate CPTX-1532 Cells. Stearns, M.E., Kim, G., Garcia, F., Wang, M. Mol. Cancer Res. (2004) [Pubmed]
  23. Assignment of UCK2, ATF3 and RGS18 from human chromosome 1 to porcine chromosomes 4, 9 and 10 with somatic and radiation hybrid panels. Aldenhoven, J., Chen, Y., Moran, C. Cytogenet. Genome Res. (2006) [Pubmed]
  24. Novel interactions between human T-cell leukemia virus type I Tax and activating transcription factor 3 at a cyclic AMP-responsive element. Low, K.G., Chu, H.M., Schwartz, P.M., Daniels, G.M., Melner, M.H., Comb, M.J. Mol. Cell. Biol. (1994) [Pubmed]
  25. Wounding activates p38 map kinase and activation transcription factor 3 in leading keratinocytes. Harper, E.G., Alvares, S.M., Carter, W.G. J. Cell. Sci. (2005) [Pubmed]
  26. Expression of transcriptional repressor ATF3/LRF1 in human atherosclerosis: colocalization and possible involvement in cell death of vascular endothelial cells. Nawa, T., Nawa, M.T., Adachi, M.T., Uchimura, I., Shimokawa, R., Fujisawa, K., Tanaka, A., Numano, F., Kitajima, S. Atherosclerosis (2002) [Pubmed]
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