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Induction of SOX4 by DNA damage is critical for p53 stabilization and function.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 3/10/2009, Vol. 106 Issue 10, p3788-3793, 6p, 6 Graphs
- Publication Year :
- 2009
-
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 50X4, 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 50X4 as a potential key factor in regulating DDR-associated cancer. [ABSTRACT FROM AUTHOR]
- Subjects :
- DNA damage
CARCINOGENESIS
GENE expression
P53 protein
TUMORS
CANCER
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 106
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 37036886
- Full Text :
- https://doi.org/10.1073/pnas.0810147106