Premium
Regulation of p53 stability and function by the deubiquitinating enzyme USP42
Author(s) -
Hock Andreas K,
Vigneron Arnaud M,
Carter Stephanie,
Ludwig Robert L,
Vousden Karen H
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.419
Subject(s) - deubiquitinating enzyme , biology , ubiquitin ligase , ubiquitin , mdm2 , transcription factor , microbiology and biotechnology , transcription (linguistics) , cell cycle , cell cycle checkpoint , suppressor , ubiquitin conjugating enzyme , apoptosis , gene , biochemistry , linguistics , philosophy
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.