Regulation and function of the p53 tumor suppressor protein

Ryan, Kevin M.; Phillips, Andrew C.; Vousden, Karen H.

doi:10.1016/s0955-0674(00)00216-7

Cited by 633 publications

(494 citation statements)

References 65 publications

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“…As noted earlier, genes encoding two tumor suppressor proteins-p.53 and pRB-are pivotal for establishing and maintaining cellular senescence. p53, a multifunctional transcriptional regulator (Sherr, 1998;Prives and Hall, 1999;Ryan et al, 2001;Wahl and Carr, 2001;Hofseth et al, 2004), is of particular interest because it is dispensable for mammalian embryogenesis and postnatal development, but crucial for preventing cancer. Indeed, most, if not all, malignant tumors harbor mutations in p53 or one of its critical regulators.…”

Section: Do Gatekeeper Tumor Suppressors Promote Aging?mentioning

confidence: 99%

Aging, tumor suppression and cancer: high wire-act!

Campisi

2005

Mechanisms of Ageing and Development

155

120

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Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responsesapoptosis or senescence-that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation. We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic pleiotropyprotecting organisms from cancer early in life, but promoting aging phenotypes, including late life cancer, in older organisms. # 2004 Published by Elsevier Ireland Ltd.

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Section: Do Gatekeeper Tumor Suppressors Promote Aging?mentioning

confidence: 99%

Aging, tumor suppression and cancer: high wire-act!

Campisi

2005

Mechanisms of Ageing and Development

155

120

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“…Many other nucleolar proteins that can move in and out of the nucleolus for controlling the stability of tumor suppressor, p53, are presented below. The p53 protein has been known as a "guardian of the genome" because of its important role in coordinating cellular responses to stress [25,26]. Its activity is regulated by changing the balance between its synthesis and degradation.…”

Section: Plurifunctionality Of the Nucleolusmentioning

confidence: 99%

The nucleolus: reviewing oldies to have new understandings

Lee

Lai

2006

Cell Res

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“…Both processes are controlled by the p53 tumor suppressor protein [109][110][111][112][113]. p53 is a transcriptional regulator that both transactivates and transrepresses target genes in response to stress [114,115]. These target genes, in turn, stimulate DNA repair, transient cell cycle arrest, permanent cell cycle arrest (senescence) or cell death (apoptosis), depending on cell type, degree and type of damage, and other variables.…”

Section: Cellular Tumor Suppressive Responsesmentioning

confidence: 99%

Cancer and aging: the importance of telomeres in genome maintenance

Rodier

Kim

Nijjar

et al. 2005

The International Journal of Biochemistry & Cell Biology

120

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Telomeres are the specialized DNA-protein structures that cap the ends of linear chromosomes, thereby protecting them from degradation and fusion by cellular DNA repair processes. In vertebrate cells, telomeres consist of several kilobase pairs of DNA having the sequence TTAGGG, a few hundred base pairs of single-stranded DNA at the 3' end of the telomeric DNA tract, and a host of proteins that organize the telomeric double and single stranded DNA into a protective structure.

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Regulation and function of the p53 tumor suppressor protein

Cited by 633 publications

References 65 publications

Aging, tumor suppression and cancer: high wire-act!

Aging, tumor suppression and cancer: high wire-act!

The nucleolus: reviewing oldies to have new understandings

Cancer and aging: the importance of telomeres in genome maintenance

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