p53 在细胞衰老调控中的作用。

Role of p53 in the Regulation of Cellular Senescence.

机构信息

Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.

Department of Medical Biotechnologies, University of Siena, 67100 Siena, Italy.

出版信息

Biomolecules. 2020 Mar 8;10(3):420. doi: 10.3390/biom10030420.

DOI:10.3390/biom10030420

PMID:32182711

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7175209/

Abstract

The p53 transcription factor plays a critical role in cellular responses to stress. Its activation in response to DNA damage leads to cell growth arrest, allowing for DNA repair, or directs cellular senescence or apoptosis, thereby maintaining genome integrity. Senescence is a permanent cell-cycle arrest that has a crucial role in aging, and it also represents a robust physiological antitumor response, which counteracts oncogenic insults. In addition, senescent cells can also negatively impact the surrounding tissue microenvironment and the neighboring cells by secreting pro-inflammatory cytokines, ultimately triggering tissue dysfunction and/or unfavorable outcomes. This review focuses on the characteristics of senescence and on the recent advances in the contribution of p53 to cellular senescence. Moreover, we also discuss the p53-mediated regulation of several pathophysiological microenvironments that could be associated with senescence and its development.

摘要

p53 转录因子在细胞对应激的反应中起着关键作用。它在响应 DNA 损伤时的激活会导致细胞生长停滞，从而允许进行 DNA 修复，或者促使细胞衰老或凋亡，从而维持基因组完整性。衰老（senescence）是一种永久性的细胞周期停滞，它在衰老过程中起着至关重要的作用，也是一种强大的生理性抗肿瘤反应，可以对抗致癌损伤。此外，衰老细胞还可以通过分泌促炎细胞因子对周围组织微环境和邻近细胞产生负面影响，最终导致组织功能障碍和/或不良后果。本综述重点关注衰老的特征以及 p53 对细胞衰老的贡献的最新进展。此外，我们还讨论了 p53 介导的对几种可能与衰老及其发展相关的病理生理微环境的调节。