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The guardian's choice: How p53 enables context-specific decision making in individual cells.

Friedel, Laura and Loewer, Alexander (2021):
The guardian's choice: How p53 enables context-specific decision making in individual cells.
In: The FEBS journal, ISSN 1742-4658,
DOI: 10.1111/febs.15767,
[Article]

Abstract

p53 plays a central role in defending the genomic integrity of our cells. In response to genotoxic stress, this tumour suppressor orchestrates the expression of hundreds of target genes, which induce a variety of cellular outcomes ranging from damage repair to induction of apoptosis. In this review, we examine how the p53 response is regulated on several levels in individual cells to allow precise and context-specific fate decisions. We discuss that the p53 response is not only controlled by its canonical regulators but also by interconnected signalling pathways that influence the dynamics of p53 accumulation upon damage and modulate its transcriptional activity at target gene promoters. Additionally, we consider how the p53 response is diversified through a variety of mechanisms at the promoter level and beyond to induce context-specific outcomes in individual cells. These layers of regulation allow p53 to react in a stimulus-specific manner and fine-tune its signaling according to the individual needs of a given cell, enabling it to take the right decision on survival or death.

Item Type: Article
Erschienen: 2021
Creators: Friedel, Laura and Loewer, Alexander
Title: The guardian's choice: How p53 enables context-specific decision making in individual cells.
Language: English
Abstract:

p53 plays a central role in defending the genomic integrity of our cells. In response to genotoxic stress, this tumour suppressor orchestrates the expression of hundreds of target genes, which induce a variety of cellular outcomes ranging from damage repair to induction of apoptosis. In this review, we examine how the p53 response is regulated on several levels in individual cells to allow precise and context-specific fate decisions. We discuss that the p53 response is not only controlled by its canonical regulators but also by interconnected signalling pathways that influence the dynamics of p53 accumulation upon damage and modulate its transcriptional activity at target gene promoters. Additionally, we consider how the p53 response is diversified through a variety of mechanisms at the promoter level and beyond to induce context-specific outcomes in individual cells. These layers of regulation allow p53 to react in a stimulus-specific manner and fine-tune its signaling according to the individual needs of a given cell, enabling it to take the right decision on survival or death.

Journal or Publication Title: The FEBS journal
Divisions: 10 Department of Biology
10 Department of Biology > Systems Biology of the Stress Response
Date Deposited: 23 Feb 2021 07:38
DOI: 10.1111/febs.15767
Identification Number: pmid:33590949
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