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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

Orphan nuclear receptor PNR/NR2E3 stimulates p53 functions by enhancing p53 acetylation

Zhi Wen1, Dohun Pyeon, Yidan Wang

  • 1McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Molecular and Cellular Biology
|October 26, 2011
PubMed

Insights

Photoreceptor-specific nuclear receptor (PNR) enhances tumor suppressor p53 activity by increasing its stability and acetylation. This discovery offers a potential new target for p53-associated cancer therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Inactivation of tumor suppressor p53 is common in human cancers.
  • Restoring p53 function is a key goal in cancer therapy.

Purpose of the Study:

  • Identify novel regulators of p53.
  • Investigate the role of photoreceptor-specific nuclear receptor (PNR)/NR2E3 in p53 regulation.

Main Methods:

  • High-throughput genetic screen to identify p53 regulators.
  • Assays in HeLa cells to assess PNR's effect on p53-responsive promoters and apoptosis.
  • Analysis of p53 protein stability, acetylation, and target gene expression.
  • Co-immunoprecipitation to study protein complex formation.

Main Results:

  • PNR was identified as a positive regulator of p53.
  • PNR stimulates p53-responsive promoters and induces apoptosis.
  • PNR enhances p53 protein stability and transcriptional activity.
  • PNR forms complexes with p53 and p300, promoting p53 acetylation and increasing expression of a subset of p53 target genes.

Conclusions:

  • PNR uniquely stimulates p53 acetylation and function.
  • PNR is a potential therapeutic target and tool for p53-associated cancer therapy.
  • PNR's role in retinal diseases due to mutation warrants further investigation.

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