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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53 and stem cells: new developments and new concerns
1Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.
Abstract:
As the guardian of the genome, the tumor suppressor p53 prevents the accumulation of genetic mutations by inducing cell cycle arrest, apoptosis or senescence of somatic cells after genotoxic and oncogenic stresses. Recent studies have identified the roles of p53 in suppressing pluripotency and cellular dedifferentiation. In this context, p53 suppresses the self-renewal of embryonic stem cells after DNA damage and blocks the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). If the inactivation of p53 pathway is a prerequisite for successful reprogramming, these findings raise concerns for the genomic stability and tumorigenecity of iPSCs and their derivatives. Elucidation of the roles of p53 as a barrier to pluripotency and cellular dedifferentiation might also reveal the mechanisms by which p53 coordinates tumor suppression and aging.
Insights
The tumor suppressor p53 prevents genetic mutations and suppresses pluripotency. Its inactivation is crucial for induced pluripotent stem cells (iPSCs), raising concerns about iPSC genomic stability and tumorigenecity.
Area of Science:
- Molecular Biology
- Cancer Research
- Stem Cell Biology
Background:
- The tumor suppressor p53 acts as the guardian of the genome, preventing genetic mutations by inducing cell cycle arrest, apoptosis, or senescence in response to cellular stress.
- Emerging research highlights p53's role in inhibiting pluripotency and cellular dedifferentiation processes.
Purpose of the Study:
- To investigate the role of p53 as a barrier to pluripotency and cellular dedifferentiation.
- To understand the implications of p53's function in the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs).
Main Methods:
- Review of recent studies on p53 function in embryonic stem cells and somatic cell reprogramming.
- Analysis of the impact of p53 inactivation on the generation and characteristics of iPSCs.
Main Results:
- p53 actively suppresses the self-renewal of embryonic stem cells following DNA damage.
- p53 inhibits the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs).
- Inactivation of the p53 pathway appears necessary for successful cellular reprogramming.
Conclusions:
- The findings suggest that p53 acts as a significant barrier to achieving pluripotency and dedifferentiation.
- The necessity of p53 inactivation for reprogramming raises critical questions regarding the genomic stability and tumorigenic potential of iPSCs and their derivatives.
- Further elucidation of p53's role may uncover mechanisms linking tumor suppression and aging.
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