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

Xin Pan, Jie Zhao, Wei Na Zhang, Hui Yan Li, Rui Mu, Tao Zhou, Hai Ying Zhang, Wei Li Gong, Ming Yu, Jiang Hong Man, Pei Jing Zhang, Ai Ng Li, Xue Min Zhang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3788-3793
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number10
DOIs
StatePublished - Mar 10 2009

Keywords

  • Mdm2
  • Tumorigenesis
  • Ubiquitination

ASJC Scopus subject areas

  • General

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