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Negative control of the Myc protein by the stress-responsive kinase Pak2

Zhongdong Huang1, Jolinda A Traugh, J Michael Bishop

  • 1The George Williams Hooper Foundation, University of California, San Francisco, California 94143-0552, USA. huangzd@itsa.ucsf.edu

Molecular and Cellular Biology
|January 30, 2004
PubMed

Insights

Pak2 phosphorylates the Myc protein at three key sites, inhibiting its DNA binding and transcriptional activity. This suggests Pak2 acts as a tumor suppressor by negatively regulating Myc in cellular stress responses.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Pak2 is a serine/threonine kinase involved in cellular stress response.
  • Myc is a proto-oncogene protein crucial for cell growth and proliferation.

Purpose of the Study:

  • To investigate the interaction between Pak2 and Myc.
  • To determine how Pak2 affects Myc function.

Main Methods:

  • In vitro and in vivo experiments were used to analyze Pak2-mediated phosphorylation of Myc.
  • DNA binding assays and transcriptional activity assays were performed.

Main Results:

  • Pak2 phosphorylates Myc at T358, S373, and T400.
  • Phosphorylation reduces Myc's DNA binding affinity by affecting dimerization and direct DNA interaction.
  • Pak2-mediated phosphorylation inhibits Myc's ability to activate transcription, promote proliferation, induce transformation, and elicit apoptosis.

Conclusions:

  • Pak2 negatively regulates Myc function.
  • Inhibition of Myc by Pak2 is implicated in the cellular stress response.
  • Pak2 may function as a tumor suppressor gene product.

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