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.
Highlights
The concept of cellular senescence was initially introduced several decades ago by Leonard Hayflick [1]
Cellular senescence is a physiological mechanism adopted by cells to limit tumorigenesis [99,100], and for this reason, a therapy-induced senescence was considered as an alternative and possibly safer approach to the traditional cancer therapy, which aimed at inducing extensive DNA damage [101]
It is abundantly clear that the cellular responses to p53 activation depend on multiple factors, including the nature of the cell stressors (e.g., DNA damaging radiation, chemicals, telomere erosion, oxidative stress, osmotic shock, deregulated oncogene expression, ribonucleotide depletion), the cell lineage, the cell physiological conditions, and the cellular environment
Summary
The concept of cellular senescence was initially introduced several decades ago by Leonard Hayflick [1]. Senescence is considered an irreversible process of growth arrest occurring in response to cellular aging as well as to various sources of cellular stimulations, including activated oncogenes, cytokines, reactive oxygen species, DNA damage, or nucleotide depletion [5,6,7]. This form of senescence is known as stress-induced premature senescence (SIPS) and has broad implications in health and diseases [8,9]. We provide an overview on the regulation of p53-mediated cellular senescence in the context of different pathophysiological conditions
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