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p53 in health and disease

Nature Reviews Molecular Cell Biology volume 8, pages 275–283 (2007)Cite this article

Key Points

  • p53 is an important tumour-suppressor protein that is altered in most cancers.

  • p53 activates various responses, including cell-cycle arrest and apoptosis. Each of these appears to contribute to tumour suppression.

  • p53 responds to both acute stress, such as genotoxic stress and the activation of oncogenes, and constitutive stress induced by factors such as hypoxia or starvation stress. Each of these can contribute to tumour development.

  • In addition to tumour suppression, p53 can also have a role in normal development, during which loss of p53 can be detrimental.

  • The activation of p53 can have undesirable effects that might contribute to diseases such as neurodegenerative syndromes and also to the ageing process in an organism.

Abstract

As a component of the response to acute stress, p53 has a well established role in protecting against cancer development. However, it is now becoming clear that p53 can have a much broader role and can contribute to the development, life expectancy and overall fitness of an organism. Although the function of p53 as a tumour suppressor ensures that we can't live without it, an integrated view of p53 suggests that not all of its functions are conducive to a long and healthy life.

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Figure 1: Activation and functions of p53.
Figure 2: Structure of p53 family members.
Figure 3: p53 and metabolism.
Figure 4: Regulation of life and death by p53.
Figure 5: Temporal regulation of p53 activity in response to DNA damage.

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Authors and Affiliations

  1. Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, G61 1BD, Glasgow, UK

    Karen H. Vousden

  2. Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore, 138673

    David P. Lane

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  1. Karen H. Vousden
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Correspondence to Karen H. Vousden.

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DATABASES

OMIM

Alzheimer's disease

Huntington disease

Li–Fraumeni syndrome

Parkinson's disease

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Glossary

ChIP analysis

A chromatin immuno-precipitation technique that identifies proteins that are bound to promoter sequences of genes in the context of endogenous chromatin.

Glycolysis

The metabolic pathway through which glucose is metabolized to provide energy.

Autophagy

A process in which parts of the cytoplasm, including the organelles it contains, are engulfed inside a membranous compartment and targeted to lysosomes for degradation.

BCL2 family

A family of proteins that share structural motifs and have an important role in positively and negatively regulating mitochondrial apoptotic pathways.

PUMA

(p53-upregulated mediator of apoptosis). A protein that belongs to the BCL2 family and that promotes mitochondrial outer membrane permeabilization and apoptosis.

Ubiquitin ligase

An enzyme that can transfer ubiquitin onto a protein, which can target the protein for degradation by the proteasome.

MDM2

A ubiquitin ligase that functions as an important negative regulator of p53. As the product of a p53-inducible gene, MDM2 functions in a negative-feedback loop with p53.

Warburg effect

An increase in aerobic glycolysis that is characteristic of cancer cells.

TIGAR

A gene that encodes a protein that functions to lower intracellular reactive oxygen species levels by enhancing the pentose phosphate pathway.

Pentose phosphate pathway

An alternative pathway for glucose metabolism that generates NADPH, which is needed for the scavenging of reactive oxygen species by reduced glutathione.

Sestrins

A family of proteins that modulate peroxide signalling and regulate intracellular reactive oxygen species levels.

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Vousden, K., Lane, D. p53 in health and disease. Nat Rev Mol Cell Biol 8, 275–283 (2007). https://doi.org/10.1038/nrm2147

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