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
相关论文
共 50 条
  • [21] The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and degradation
    Louria-Hayon, I
    Grossman, T
    Sionov, RV
    Alsheich, O
    Pandolfi, PP
    Haupt, Y
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (35) : 33134 - 33141
  • [22] Mechanistic studies of MDM2-mediated ubiquitination in p53 regulation
    Brooks, Christopher L.
    Li, Muyang
    Gu, Wei
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (31) : 22804 - 22815
  • [23] MDM2-mediated degradation of WRN promotes cellular senescence in a p53-independent manner
    Liu, Boya
    Yi, Jingjie
    Yan, Xin
    Liu, Lu
    Lou, Xinlin
    Zhang, Zeyuan
    Qi, Hao
    Wang, Zhe
    Zou, Junhua
    Zhu, Wei-Guo
    Gu, Wei
    Luo, Jianyuan
    [J]. ONCOGENE, 2019, 38 (14) : 2501 - 2515
  • [24] MDM2-mediated degradation of WRN promotes cellular senescence in a p53-independent manner
    Boya Liu
    Jingjie Yi
    Xin Yang
    Lu Liu
    Xinlin Lou
    Zeyuan Zhang
    Hao Qi
    Zhe Wang
    Junhua Zou
    Wei-Guo Zhu
    Wei Gu
    Jianyuan Luo
    [J]. Oncogene, 2019, 38 : 2501 - 2515
  • [25] Erratum: p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug
    Shu-Ping Wang
    Wen-Lung Wang
    Yih-Leong Chang
    Chen-Tu Wu
    Yu-Chih Chao
    Shih-Han Kao
    Ang Yuan
    Chung-Wu Lin
    Shuenn-Chen Yang
    Wing-Kai Chan
    Ker-Chau Li
    Tse-Ming Hong
    Pan-Chyr Yang
    [J]. Nature Cell Biology, 2009, 11 (7) : 914 - 914
  • [26] MYL6B, a myosin light chain, promotes MDM2-mediated p53 degradation and drives HCC development
    Xingwang Xie
    Xueyan Wang
    Weijia Liao
    Ran Fei
    Nan Wu
    Xu Cong
    Qian Chen
    Lai Wei
    Yu Wang
    Hongsong Chen
    [J]. Journal of Experimental & Clinical Cancer Research, 37
  • [27] Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5
    Dai, MS
    Lu, H
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (43) : 44475 - 44482
  • [28] MDM2 chaperones the p53 tumor suppressor
    Wawrzynow, Bartosz
    Zylicz, Alicja
    Wallace, Maura
    Hupp, Ted
    Zylicz, Maciej
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (45) : 32603 - 32612
  • [29] MYL6B, a myosin light chain, promotes MDM2-mediated p53 degradation and drives HCC development
    Xie, Xingwang
    Wang, Xueyan
    Liao, Weijia
    Fei, Ran
    Wu, Nan
    Cong, Xu
    Chen, Qian
    Wei, Lai
    Wang, Yu
    Chen, Hongsong
    [J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2018, 37
  • [30] P53 stability and activity is regulated by Mdm2-mediated induction of alternative p53 translation products
    Yin, YL
    Luciani, MG
    Fåhraeus, R
    [J]. NATURE CELL BIOLOGY, 2002, 4 (06) : 462 - 467