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

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.

SUBMITTER: Pan X

PROVIDER: S-EPMC2656158 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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

Pan Xin X Zhao Jie J Zhang Wei-Na WN Li Hui-Yan HY Mu Rui R Zhou Tao T Zhang Hai-Ying HY Gong Wei-Li WL Yu Ming M Man Jiang-Hong JH Zhang Pei-Jing PJ Li Ai-Ling AL Zhang Xue-Min XM

Proceedings of the National Academy of Sciences of the United States of America 20090220 10

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 ...[more]

PMID: 19234109

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