ASK1-signaling promotes c-Myc protein stability during apoptosis

Kohji Noguchi, Akiko Kokubu, Chifumi Kitanaka, Hidenori Ichijo, Yoshiyuki Kuchino

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

We previously reported that JNK is involved in the regulation of c-Myc-mediated apoptosis triggered by UV irradiation and anticancer drug treatment. Here we show that ASK1 is an upstream regulator for c-Myc-mediated apoptosis triggered by UV, and we found a direct role for Ser-62 and Ser-71 in the regulation of protein stability and function of c-Myc. The ASK1-JNK pathway enhanced the protein stability of c-Myc through phosphorylation at Ser-62 and Ser-71, which was required for c-Myc-dependent apoptosis by ASK1-signaling. Interestingly, ASK1-signaling attenuated the degradation of ubiquitinated c-Myc without affecting the ubiquitination process. Together, these findings indicate that the ASK1-JNK pathway promotes the proapoptotic activity of c-Myc by modulating c-Myc protein stability through phosphorylation at Ser-62 and Ser-71.

Original languageEnglish
Pages (from-to)1313-1320
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume281
Issue number5
DOIs
Publication statusPublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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