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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

ASK1-signaling promotes c-Myc protein stability during apoptosis

K Noguchi1, A Kokubu, C Kitanaka

  • 1Department of Bioactive Molecules, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan. knoguchi@nih.go.jp

Biochemical and Biophysical Research Communications
|March 13, 2001
PubMed

Insights

The ASK1-JNK pathway stabilizes c-Myc protein via phosphorylation, enhancing c-Myc-dependent apoptosis. This mechanism involves regulating c-Myc protein stability, not ubiquitination, in response to UV radiation.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Apoptosis Research

Background:

  • Previous work identified c-Jun N-terminal kinase (JNK) involvement in c-Myc-mediated apoptosis.
  • Apoptosis is a critical cellular process regulated by various signaling pathways.
  • c-Myc is a proto-oncogene implicated in cell proliferation, differentiation, and apoptosis.

Purpose of the Study:

  • To elucidate the upstream regulators of c-Myc-mediated apoptosis.
  • To investigate the role of specific phosphorylation sites in c-Myc regulation.
  • To understand how the ASK1-JNK pathway influences c-Myc protein stability and function.

Main Methods:

  • Investigated the ASK1-JNK signaling pathway's role in UV-induced apoptosis.
  • Analyzed the phosphorylation of c-Myc at Serine 62 (Ser-62) and Serine 71 (Ser-71).
  • Assessed the impact of ASK1 signaling on c-Myc ubiquitination and degradation.

Main Results:

  • Apoptosis signal-regulating kinase 1 (ASK1) acts upstream of JNK in UV-induced c-Myc apoptosis.
  • Phosphorylation of c-Myc at Ser-62 and Ser-71 by the ASK1-JNK pathway enhances c-Myc protein stability.
  • ASK1 signaling reduces the degradation of ubiquitinated c-Myc without altering ubiquitination levels.

Conclusions:

  • The ASK1-JNK pathway promotes c-Myc-dependent apoptosis by increasing c-Myc protein stability.
  • Phosphorylation at Ser-62 and Ser-71 is crucial for c-Myc stabilization and proapoptotic function.
  • This pathway represents a key regulatory mechanism controlling c-Myc's role in apoptosis.

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