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Regulation of p53 stability and function by the deubiquitinating enzyme USP42.

ABSTRACT: The p53 tumour suppressor protein is a transcription factor that prevents oncogenic progression by activating the expression of apoptosis and cell-cycle arrest genes in stressed cells. The stability of p53 is tightly regulated by ubiquitin-dependent degradation, driven mainly by the ubiquitin ligase MDM2. In this study, we have identified USP42 as a DUB that interacts with and deubiquitinates p53. USP42 forms a direct complex with p53 and controls level of ubiquitination during the early phase of the response to a range of stress signals. Although we do not find a clear role for USP42 in controlling either the basal or fully activated levels of p53, the function of USP42 is required to allow the rapid activation of p53-dependent transcription and a p53-dependent cell-cycle arrest in response to stress. These functions of USP42 are likely to contribute to the repair and recovery of cells from mild or transient damage.

SUBMITTER: Hock AK

PROVIDER: S-EPMC3243628 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Regulation of p53 stability and function by the deubiquitinating enzyme USP42.

Hock Andreas K AK Vigneron Arnaud M AM Carter Stephanie S Ludwig Robert L RL Vousden Karen H KH

The EMBO journal 20111115 24

The p53 tumour suppressor protein is a transcription factor that prevents oncogenic progression by activating the expression of apoptosis and cell-cycle arrest genes in stressed cells. The stability of p53 is tightly regulated by ubiquitin-dependent degradation, driven mainly by the ubiquitin ligase MDM2. In this study, we have identified USP42 as a DUB that interacts with and deubiquitinates p53. USP42 forms a direct complex with p53 and controls level of ubiquitination during the early phase o ...[more]

PMID: 22085928

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