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

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.
Mesh Terms:
Acetylation, Apoptosis, Cell Cycle, Cell Line, Tumor, Cell Proliferation, DNA Damage, Humans, Protein Binding, Protein Stability, Proto-Oncogene Proteins c-mdm2, SOXC Transcription Factors, Tumor Suppressor Protein p53, Ubiquitination
Proc. Natl. Acad. Sci. U.S.A.
Date: Mar. 10, 2009
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