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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. 106(10)
- 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 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.
- Subjects :
- Cell cycle checkpoint
DNA damage
Apoptosis
Biology
medicine.disease_cause
SOXC Transcription Factors
Proto-Oncogene Proteins c-mdm2
Ubiquitin
Cell Line, Tumor
medicine
Humans
Cell Proliferation
Multidisciplinary
Protein Stability
Cell Cycle
Ubiquitination
Acetylation
Cell cycle
Biological Sciences
body regions
biology.protein
Cancer research
Mdm2
Tumor Suppressor Protein p53
Carcinogenesis
DNA Damage
Protein Binding
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 106
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....a752b82f59a5168d62aee5ec5ae85fa9