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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

Rap2b, a novel p53 target, regulates p53-mediated pro-survival function

Xinyue Zhang1, Yunlong He, Kyoung-Hwa Lee

  • 1Cancer and Stem Cell Epigenetics, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

Cell Cycle (Georgetown, Tex.)
|March 29, 2013
PubMed

Insights

The tumor suppressor p53 normally balances cell survival and apoptosis. Researchers found Rap2b, a p53-activated gene, promotes cell survival and may be a target to enhance cancer therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • The tumor suppressor p53 is a key regulator of cellular responses to DNA damage, including apoptosis and cell cycle arrest.
  • The balance between pro-survival and pro-apoptotic pathways dictates the cell's fate after DNA damage.
  • Identifying p53 downstream targets involved in this decision is crucial.

Purpose of the Study:

  • To identify novel p53 downstream genes that regulate the cell fate decision between apoptosis and survival after DNA damage.
  • To investigate the role of Rap2b in the p53-mediated cellular response to DNA damage.

Main Methods:

  • Integrative genomic analysis to identify p53-activated genes.
  • ChIP assays to confirm p53 binding to the Rap2b promoter.
  • Small interfering RNA (siRNA) to reduce Rap2b levels.
  • Analysis of cancer genomic data.
  • Anchorage-independent growth assays.

Main Results:

  • Rap2b was identified as a conserved p53-activated gene.
  • p53 directly binds to the Rap2b promoter and activates its transcription upon DNA damage.
  • Reducing Rap2b levels sensitized cells to DNA damage-induced apoptosis in a p53-dependent manner.
  • Rap2b is overexpressed in various human tumors.
  • Rap2b exhibits weak transformation activity.

Conclusions:

  • Rap2b acts as a pro-survival factor in the p53 pathway, counteracting apoptosis after DNA damage.
  • Rap2b is a novel component of the p53-mediated pro-survival program.
  • Targeting Rap2b could potentially sensitize tumor cells to DNA damage-induced apoptosis.
Keywords:
chromatinepigeneticsgene regulationp53

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