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Updated: May 12, 2026
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
Summary
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.
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