title: Induction of SOX4 by DNA damage is critical for p53 stabilization and function.
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.
authors.affiliation: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Tai-Ping Road 27, Beijing 100850, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Pan
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Zhang
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Mu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zhang
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Gong
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Jiang-Hong
authors.initials: JH
authors.lastname: Man
authors.forename: Pei-Jing
authors.initials: PJ
authors.lastname: Zhang
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Li
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Zhang
mesh_terms: 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
chemical_list: C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2