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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

p53 binds to and is required for the repression of Arf tumor suppressor by HDAC and polycomb

Yaxue Zeng1, Yojiro Kotake, Xin-Hai Pei

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Cancer Research
|March 31, 2011
PubMed

Insights

The tumor suppressor Arf is normally repressed but activated by cancer-causing insults. Our study shows p53 protein recruits HDAC and PcG proteins to repress Arf expression, forming a crucial feedback loop.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Biology

Background:

  • The tumor suppressor Arf's expression is tightly repressed in young cells but activated by oncogenic insults and during aging.
  • This activation leads to p53 activation and cell-cycle arrest, preventing hyperproliferation.
  • The precise mechanisms of Arf's transcriptional repression and activation remain unclear.

Purpose of the Study:

  • To elucidate the mechanisms underlying the transcriptional repression of the Arf gene.
  • To investigate the role of p53, histone deacetylases (HDAC), and polycomb group (PcG) proteins in Arf regulation.

Main Methods:

  • Studied Arf expression in mouse embryonic fibroblasts (MEFs) and p53 null mice.
  • Utilized techniques to assess p53 binding, DNA binding activity, and transactivation.
  • Investigated the recruitment of HDAC and PcG proteins to the Arf locus.

Main Results:

  • p53 binds to and represses Arf expression, requiring both DNA binding and transactivation activities.
  • This repression is dependent on the function of histone deacetylases (HDAC) and polycomb group (PcG) proteins.
  • p53 recruits HDAC and PcG to the Arf locus, and its inactivation disrupts this binding.

Conclusions:

  • p53 actively represses Arf transcription by recruiting HDAC and PcG proteins to the Arf locus.
  • This repression represents a novel feedback loop in p53-mediated regulation.
  • Understanding this mechanism is crucial for comprehending cell-cycle control and tumor suppression.

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