Mouse models of p53 functions.

Research output: Contribution to journalReview articlepeer-review

79 Scopus citations

Abstract

Studies in mice have yielded invaluable insight into our understanding of the p53 pathway. Mouse models with activated p53, no p53, and mutant p53 have queried the role of p53 in development and tumorigenesis. In these models, p53 is activated and stabilized via redundant posttranslational modifications. On activation, p53 initiates two major responses: inhibition of proliferation (via cell-cycle arrest, quiescence, senescence, and differentiation) and induction of apoptosis. Importantly, these responses are cell-type and tumor-type-specific. The analysis of mutant p53 alleles has established a gain-of-function role for p53 mutants in metastasis. The development of additional models that can precisely time the oncogenic events in single cells will provide further insight into the evolution of tumors, the importance of the stroma, and the cooperating events that lead to disruption of the p53 pathway. Ultimately, these models should serve to study the effects of novel drugs on tumor response as well as normal homeostasis.

Original languageEnglish (US)
Pages (from-to)a001115
JournalCold Spring Harbor Perspectives in Biology
Volume2
Issue number4
DOIs
StatePublished - Apr 1 2010

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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