Review Article | Published:

The multiple mechanisms that regulate p53 activity and cell fate

Abstract

The tumour suppressor p53 has a central role in the response to cellular stress. Activated p53 transcriptionally regulates hundreds of genes that are involved in multiple biological processes, including in DNA damage repair, cell cycle arrest, apoptosis and senescence. In the context of DNA damage, p53 is thought to be a decision-making transcription factor that selectively activates genes as part of specific gene expression programmes to determine cellular outcomes. In this Review, we discuss the multiple molecular mechanisms of p53 regulation and how they modulate the induction of apoptosis or cell cycle arrest following DNA damage. Specifically, we discuss how the interaction of p53 with DNA and chromatin affects gene expression, and how p53 post-translational modifications, its temporal expression dynamics and its interactions with chromatin regulators and transcription factors influence cell fate. These multiple layers of regulation enable p53 to execute cellular responses that are appropriate for specific cellular states and environmental conditions.

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Acknowledgements

The authors thank members of the Lahav laboratory for helpful comments on the manuscript. Research in the Lahav laboratory is supported by grants from the US National Institutes of Health (GM083303 and GM116864).

Reviewer information

Nature Reviews Molecular Cell Biology thanks M. Barton and other anonymous reviewer(s) for their contribution to the peer review of this work.

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All authors made substantial contributions to the discussion of content, wrote the manuscript and edited it before submission. A.H., A.J. and G.L. also researched data for the article.

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The authors declare no competing interests.

Correspondence to Galit Lahav.

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Fig. 1: The p53 binding site.
Fig. 2: Regulation of p53 target genes by post-translational modification and interactions with chromatin regulators and transcription factors.
Fig. 3: p53 dynamics regulate gene expression.
Fig. 4: Regulation of p53-mediated cell fate outcomes.