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.
Pan
Xin
X
Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Tai-Ping Road 27, Beijing 100850, China.
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
D000107:Acetylation; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004249:DNA Damage; D006801:Humans; D011485:Protein Binding; D055550:Protein Stability; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054875:Ubiquitination
C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2