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

Published on: August 4, 2019

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Targeting cellular senescence in cancer and aging: roles of p53 and its isoforms

Jessica Beck1,2, Casmir Turnquist1,3, Izumi Horikawa1

  • 1Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Carcinogenesis
|July 4, 2020
PubMed

Insights

Cellular senescence and its secretory phenotype (SASP) contribute to aging diseases. Targeting senescent cells, regulated by p53 isoforms, offers new therapeutic strategies for age-related conditions.

Area of Science:

  • Gerontology and Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • Cellular senescence and the senescence-associated secretory phenotype (SASP) are implicated in age-related diseases.
  • The TP53 gene, encoding tumor suppressor protein p53, plays a role in regulating cellular senescence.
  • p53 isoforms, generated through alternative splicing and translation, are endogenously expressed and have functional roles.

Purpose of the Study:

  • To review the mechanisms and functions of cellular senescence and SASP in health and disease.
  • To discuss the regulation of cellular senescence by p53 isoforms.
  • To explore the therapeutic potential of targeting cellular senescence for cancer- and age-associated diseases.

Main Methods:

  • Literature review of cellular senescence, SASP, and p53 research.
  • Analysis of p53 isoform generation and function.
  • Discussion of therapeutic strategies targeting senescent cells.

Main Results:

  • Cellular senescence and SASP contribute to aging and disease.
  • p53 isoforms modulate full-length p53 functions like senescence, apoptosis, and DNA repair.
  • Targeting senescent cells presents a promising therapeutic avenue.

Conclusions:

  • Understanding p53 isoform regulation of cellular senescence is crucial for therapeutic development.
  • Targeting cellular senescence offers a novel approach for treating cancer and age-related diseases.
  • This review highlights 40 years of p53 research and 15 years of p53 isoform research.

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