Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c- Jun N-terminal kinase

Kohji Noguchi, Chifumi Kitanaka, Hironobu Yamana, Akiko Kokubu, Toshihiro Mochizuki, Yoshiyuki Kuchino

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140 Citations (Scopus)

Abstract

The expression of c-myc promotes cell proliferation and also sensitizes cells to various extracellular apoptotic stimuli. However, signal pathways regulating the function of Myc proteins during apoptosis are unknown. c-Jun N-terminal kinase (JNK) is activated by various apoptotic stimuli, but neither the target molecule(s) or the action of JNK has been identified in Myc-mediated apoptosis. Here, we found that JNK selectively interacted with, and phosphorylated, c-Myc at Ser-62 and Ser-71 as confirmed with phospho-c- Myc-specific antibodies. Interestingly, dominant negative mutant JNK(APF) impaired the c-Myc-dependent apoptosis, but not mutated c-Myc (S62A/S71A)- dependent apoptosis triggered by UV irradiation. Furthermore, c-Myc (S62A/S71A)-expressing NIH3T3 cells were not sensitized like wild type c-Myc- expressing NIH3T3 cells to JNK-activating apoptotic stimuli, such as UV and Taxol. These results indicate that the JNK pathway is selectively involved in the c-Myc-mediated apoptosis and that the apoptotic function of c-Myc is directly regulated by JNK pathway through phosphorylation at Ser-62 and Ser- 71.

Original languageEnglish
Pages (from-to)32580-32587
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number46
DOIs
Publication statusPublished - 1999 Nov 12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Noguchi, K., Kitanaka, C., Yamana, H., Kokubu, A., Mochizuki, T., & Kuchino, Y. (1999). Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c- Jun N-terminal kinase. Journal of Biological Chemistry, 274(46), 32580-32587. https://doi.org/10.1074/jbc.274.46.32580