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Gene Review

Atf4  -  activating transcription factor 4

Mus musculus

Synonyms: Activating transcription factor 4, Atf-4, C/ATF, C/EBP-related ATF, CREB2, ...
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Disease relevance of Atf4


High impact information on Atf4


Biological context of Atf4


Anatomical context of Atf4


Associations of Atf4 with chemical compounds

  • Deletion analysis showed that the leucine zipper domain of ATF4 is critical for Runx2 activation [9].

Other interactions of Atf4

  • Regions within Runx2 required for ATF4 complex formation and activation were identified [9].
  • Overexpression of IMPACT in mouse embryonic fibroblasts inhibited phosphorylation of eIF2alpha by GCN2 under leucine starvation conditions, abolishing expression of its downstream target genes, ATF4 (CREB-2) and CHOP (GADD153) [13].
  • One of these is a bZIP protein of the ATF/CREB protein family--probably the murine homolog of TAXREB67 [14].
  • Microphthalmia due to p53-mediated apoptosis of anterior lens epithelial cells in mice lacking the CREB-2 transcription factor [12].
  • In addition to its own family members, ATF4 can also form heterodimers with other related but distinct bZIP proteins such as the C/EBP, AP-1 and Maf families, which may give rise to a variety of combinatorial diversity in gene regulation [2].

Analytical, diagnostic and therapeutic context of Atf4


  1. Mutated Atf4 suppresses c-Ha-ras oncogene transcript levels and cellular transformation in NIH3T3 fibroblasts. Mielnicki, L.M., Hughes, R.G., Chevray, P.M., Pruitt, S.C. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  2. Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres. Tanaka, T., Tsujimura, T., Takeda, K., Sugihara, A., Maekawa, A., Terada, N., Yoshida, N., Akira, S. Genes Cells (1998) [Pubmed]
  3. Inhibition of ATF4 transcriptional activity by FIAT/gamma-taxilin modulates bone mass accrual. Yu, V.W., Gauthier, C., St-Arnaud, R. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  4. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Yang, X., Matsuda, K., Bialek, P., Jacquot, S., Masuoka, H.C., Schinke, T., Li, L., Brancorsini, S., Sassone-Corsi, P., Townes, T.M., Hanauer, A., Karsenty, G. Cell (2004) [Pubmed]
  5. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Harding, H.P., Zhang, Y., Zeng, H., Novoa, I., Lu, P.D., Calfon, M., Sadri, N., Yun, C., Popko, B., Paules, R., Stojdl, D.F., Bell, J.C., Hettmann, T., Leiden, J.M., Ron, D. Mol. Cell (2003) [Pubmed]
  6. FIAT represses ATF4-mediated transcription to regulate bone mass in transgenic mice. Yu, V.W., Ambartsoumian, G., Verlinden, L., Moir, J.M., Prud'homme, J., Gauthier, C., Roughley, P.J., St-Arnaud, R. J. Cell Biol. (2005) [Pubmed]
  7. Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response. Lu, P.D., Harding, H.P., Ron, D. J. Cell Biol. (2004) [Pubmed]
  8. ATF4, the osteoblast accumulation of which is determined post-translationally, can induce osteoblast-specific gene expression in non-osteoblastic cells. Yang, X., Karsenty, G. J. Biol. Chem. (2004) [Pubmed]
  9. Cooperative interactions between activating transcription factor 4 and Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression. Xiao, G., Jiang, D., Ge, C., Zhao, Z., Lai, Y., Boules, H., Phimphilai, M., Yang, X., Karsenty, G., Franceschi, R.T. J. Biol. Chem. (2005) [Pubmed]
  10. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Carracedo, A., Gironella, M., Lorente, M., Garcia, S., Guzmán, M., Velasco, G., Iovanna, J.L. Cancer Res. (2006) [Pubmed]
  11. Activating transcription factor 4 overexpression inhibits proliferation and differentiation of mammary epithelium resulting in impaired lactation and accelerated involution. Bagheri-Yarmand, R., Vadlamudi, R.K., Kumar, R. J. Biol. Chem. (2003) [Pubmed]
  12. Microphthalmia due to p53-mediated apoptosis of anterior lens epithelial cells in mice lacking the CREB-2 transcription factor. Hettmann, T., Barton, K., Leiden, J.M. Dev. Biol. (2000) [Pubmed]
  13. IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation. Pereira, C.M., Sattlegger, E., Jiang, H.Y., Longo, B.M., Jaqueta, C.B., Hinnebusch, A.G., Wek, R.C., Mello, L.E., Castilho, B.A. J. Biol. Chem. (2005) [Pubmed]
  14. Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun. Chevray, P.M., Nathans, D. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  15. Transcription of human zinc finger ZNF268 gene requires an intragenic promoter element. Guo, M.X., Wang, D., Shao, H.J., Qiu, H.L., Xue, L., Zhao, Z.Z., Zhu, C.G., Shi, Y.B., Li, W.X. J. Biol. Chem. (2006) [Pubmed]
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