Abstract
The tumour suppressor p53, a stress-responsive transcription factor, plays a central role in cellular senescence. The role of p53 in senescence-associated stable proliferative arrest has been extensively studied. However, increasing evidence indicates that p53 also modulates the ability of senescent cells to produce and secrete diverse bioactive factors (collectively called the senescence-associated secretory phenotype, SASP). Senescence has been linked with both physiological and pathological conditions, the latter including ageing, cancer and other age-related disorders, in part through the SASP. Cellular functions are generally dictated by the expression profile of lineage-specific genes. Indeed, expression of SASP factors and their regulators are often biased by cell type. In addition, emerging evidence suggests that p53 contributes to deregulation of more stringent lineage-specific genes during senescence. P53 itself is also tightly regulated at the protein level. In contrast to the rapid and transient activity of p53 upon stress ('acute-p53'), during senescence and other prolonged pathological conditions, p53 activities are sustained and fine-tuned through a combination of different inputs and outputs ('chronic-p53').
Highlights
Cellular senescence is characterised by stable exit from the cell cycle in response to various stimuli, both pathological and physiological [1]
The functional relevance of extracellular vesicle (EV) in senescence and cancer and how p53 is involve in this process are extensively discussed in recent reviews [18,19,20], and we focus this section on the senescenceassociated secretory phenotype (SASP)
One striking example of context-dependent chronicp53-targets can be seen at the epidermal differentiation complex (EDC), a ~ 1.5-Mb locus containing a series of genes whose products are involved in the final stage of keratinocyte differentiation, namely cornification, a unique form of programmed cell death, which contributes to the skin barrier function [54]
Summary
Cellular senescence is characterised by stable exit from the cell cycle in response to various stimuli, both pathological and physiological [1]. Acute activation of p53 in response to cellular stress results in the expression of genes involved in diverse effector programmes, including cell cycle, DNA repair and cell death, to mitigate cellular and tissue damage [11].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
