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Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3788-93. doi: 10.1073/pnas.0810147106. Epub 2009 Feb 20.

Induction of SOX4 by DNA damage is critical for p53 stabilization and function.

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1
Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Tai-Ping Road 27, Beijing 100850, China.

Abstract

DNA damage response (DDR) acts as a tumorigenesis barrier, and any defects in the DDR machinery may lead to cancer. SOX4 expression is elevated in many types of tumors; however, its role in DDR is still largely unknown. Here, we show that SOX4, a new DNA damage sensor, is required for the activation of p53 tumor suppressor in response to DNA damage. Notably, SOX4 interacts with and stabilizes p53 protein by blocking Mdm2-mediated p53 ubiquitination and degradation. Furthermore, SOX4 enhances p53 acetylation by interacting with p300/CBP and facilitating p300/CBP/p53 complex formation. In concert with these results, SOX4 promotes cell cycle arrest and apoptosis, and it inhibits tumorigenesis in a p53-dependent manner. Therefore, these findings highlight SOX4 as a potential key factor in regulating DDR-associated cancer.

PMID:
19234109
PMCID:
PMC2656158
DOI:
10.1073/pnas.0810147106
[Indexed for MEDLINE]
Free PMC Article
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