XPC promotes MDM2-mediated degradation of the p53 tumor suppressor

被引:16
|
作者
Krzeszinski, Jing Yan [1 ,2 ]
Choe, Vitnary [2 ]
Shao, Jia [3 ]
Bao, Xin [2 ]
Cheng, Haili [2 ]
Luo, Shiwen [3 ]
Huo, Keke [1 ]
Rao, Hai [2 ]
机构
[1] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China
[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA
[3] Nanchang Univ, Affiliated Hosp 1, Nanchang 330006, Jiangxi, Peoples R China
基金
美国国家卫生研究院;
关键词
DNA-REPAIR GENES; UBIQUITIN; POLYMORPHISMS; PROTEASOME; MUTATION; DISEASE; RISK;
D O I
10.1091/mbc.E13-05-0293
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Although ubiquitin receptor Rad23 has been implicated in bringing ubiquitylated p53 to the proteasome, how Rad23 recognizes p53 remains unclear. We demonstrate that XPC, a Rad23-binding protein, regulates p53 turnover. p53 protein in XPC-deficient cells remains ubiquitylated, but its association with the proteasome is drastically reduced, indicating that XPC regulates a postubiquitylation event. Furthermore, we found that XPC participates in the MDM2-mediated p53 degradation pathway via direct interaction with MDM2. XPC W690S pathogenic mutant is specifically defective for MDM2 binding and p53 degradation. p53 is known to become stabilized following UV irradiation but can be rendered unstable by XPC overexpression, underscoring a critical role of XPC in p53 regulation. Elucidation of the proteolytic role of XPC in cancer cells will help to unravel the detailed mechanisms underlying the coordination of DNA repair and proteolysis.
引用
收藏
页码:213 / 221
页数:9
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