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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Phosphorylation
JNK Mitogen-Activated Protein Kinases
Phosphotransferases
Apoptosis
Cell proliferation
Paclitaxel
Signal Transduction
Cell Proliferation
Irradiation
Molecules
Antibodies
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

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

Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c- Jun N-terminal kinase. / Noguchi, Kohji; Kitanaka, Chifumi; Yamana, Hironobu; Kokubu, Akiko; Mochizuki, Toshihiro; Kuchino, Yoshiyuki.

In: Journal of Biological Chemistry, Vol. 274, No. 46, 12.11.1999, p. 32580-32587.

Research output: Contribution to journalArticle

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, vol. 274, no. 46, pp. 32580-32587. https://doi.org/10.1074/jbc.274.46.32580
Noguchi, Kohji ; Kitanaka, Chifumi ; Yamana, Hironobu ; Kokubu, Akiko ; Mochizuki, Toshihiro ; Kuchino, Yoshiyuki. / Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c- Jun N-terminal kinase. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 46. pp. 32580-32587.
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