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Inhibition of p53 acetylation by INHAT subunit SET/TAF-Iβ represses p53 activity

Ji-Young Kim1, Kyu-Sun Lee, Jin-Ee Seol

  • 1Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Korea.

Nucleic Acids Research
|September 14, 2011
PubMed

Insights

The histone chaperone SET/TAF-Iβ inhibits p53 acetylation, blocking stress responses like cell cycle arrest and apoptosis. This finding reveals a new regulatory mechanism for tumor suppressor p53 activation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The tumor suppressor p53 is crucial for cellular stress response.
  • Post-translational modifications, including acetylation by CBP/p300 and PCAF, regulate p53 activity.
  • Mechanisms controlling p53 acetylation remain incompletely understood.

Purpose of the Study:

  • To investigate the role of SET/TAF-Iβ in modulating p53 acetylation and activity.
  • To elucidate the impact of SET/TAF-Iβ on p53-mediated cellular responses to stress.

Main Methods:

  • Investigated SET/TAF-Iβ interaction with p53 and its effect on p53 acetylation.
  • Utilized apoptosis assays (FACS, TUNEL, BrdU incorporation) to assess cell proliferation and death.
  • Examined the effect of SET/TAF-Iβ on p53 target gene transcription.
  • Studied the role of SET/TAF-Iβ in a Drosophila model of apoptosis.

Main Results:

  • SET/TAF-Iβ directly inhibited p300- and PCAF-mediated p53 acetylation in an INHAT domain-dependent manner.
  • SET/TAF-Iβ interacted with p53, repressed p53 target gene transcription, and blocked p53-mediated cell cycle arrest and apoptosis.
  • SET/TAF-Iβ promoted cellular proliferation by inhibiting p53 acetylation.
  • SET/TAF-Iβ expression rescued UV-induced or dp53 overexpression-driven apoptosis in Drosophila, correlating with reduced dp53 acetylation.

Conclusions:

  • SET/TAF-Iβ acts as a negative regulator of p53 acetylation and function.
  • This study identifies SET/TAF-Iβ as a key modulator of stress-induced p53 activation.
  • Findings provide novel insights into the regulation of p53 by histone acetyltransferase (HAT)-inhibiting histone chaperones.

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