Stress response gene ATF3 is a target of c-myc in serum-induced cell proliferation

Kiyoshi Tamura, Bayin Hua, Susumu Adachi, Isil Guney, Junya Kawauchi, Masaki Morioka, Mimi Tamamori-Adachi, Yujiro Tanaka, Yusaku Nakabeppu, Makoto Sunamori, John M. Sedivy, Shigetaka Kitajima

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Abstract

The c-myc proto-oncogene encodes a transcription factor that promotes cell cycle progression and cell proliferation, and its deficiency results in severely retarded proliferation rates. The ATF3 stress response gene encodes a transcription factor that plays a role in determining cell fate under stress conditions. Its biological significance in the control of cell proliferation and its crosstalk regulation, however, are not well understood. Here, we report that the serum response of the ATF3 gene expression depends on c-myc gene and that the c-Myc complex at ATF/CREB site of the gene promoter plays a role in mediating the serum response. Intriguingly, ectopic expression of ATF3 promotes proliferation of c-myc-deficient cells, mostly by alleviating the impeded G1-phase progression observed in these cells, whereas ATF3 knockdown significantly suppresses proliferation of wild-type cells. Our study demonstrates that ATF3 is downstream of the c-Myc signaling pathway and plays a role in mediating the cell proliferation function of c-Myc. Our results provide a novel insight into the functional link of the stress response gene ATF3 and the protooncogene c-myc.

Original languageEnglish
Pages (from-to)2590-2601
Number of pages12
JournalEMBO Journal
Volume24
Issue number14
DOIs
Publication statusPublished - Jul 20 2005

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Tamura, K., Hua, B., Adachi, S., Guney, I., Kawauchi, J., Morioka, M., Tamamori-Adachi, M., Tanaka, Y., Nakabeppu, Y., Sunamori, M., Sedivy, J. M., & Kitajima, S. (2005). Stress response gene ATF3 is a target of c-myc in serum-induced cell proliferation. EMBO Journal, 24(14), 2590-2601. https://doi.org/10.1038/sj.emboj.7600742