NQO1 Stabilizes p53 in Response to Oncogene-Induced Senescence

被引：23
作者：
Liu, Kaiyu [1 ]
Jin, Bo [2 ]
Wu, Chenglin [3 ]
Yang, Jianming [1 ]
Zhan, Xiangwen [1 ]
Wang, Le [1 ]
Shen, Xiaomeng [1 ]
Chen, Jing [1 ]
Chen, Hao [1 ]
Mao, Zebin [1 ]
机构：
[1] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
[2] Peking Univ, Hosp 1, Dept Clin Lab, Beijing 100034, Peoples R China
[3] Navy Gen Hosp, Ctr Basic Med Sci, Beijing 100048, Peoples R China
来源：
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2015年 / 11卷 / 07期
关键词：
NQO1; p53; senescence; OXIDOREDUCTASE(1) DT-DIAPHORASE; CELLULAR SENESCENCE; PROTEASOMAL DEGRADATION; HUMAN FIBROBLASTS; HETEROCHROMATIN FORMATION; TUMOR SUPPRESSION; ACTIVATION; EXPRESSION; CANCER; CELLS;
D O I：
10.7150/ijbs.11978
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Cellular senescence is a state of permanent cellular arrest that provides an initial barrier to cell transformation and tumorigenesis. In this study, we report that expression of NAD(P)H:quinone oxidoreductase 1 (NQO1), a cytoplasmic 2-electron reductase, is induced during oncogene-induced senescence (OIS). Depletion of NQO1 resulted in the delayed onset of senescence. In contrast, ectopic expression of NQO1 enhanced the senescence phenotype. Analysis of the mechanism underlying the up-regulation of NQO1 expression during senescence identified that NQO1 promotes p53 accumulation in an MDM2 and ubiquitin independent manner, which reinforces the cellular senescence phenotype. Specifically, we demonstrated that NRF2/KEAP1 signaling regulates NQO1 expression during OIS. More importantly, we confirmed that depletion of NQO1 facilitates cell transformation and tumorigenesis, which indicates that NQO1 takes part in the senescence barrier and has anti-oncogenic properties in cell transformation.
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收藏
页码：762 / 771
页数：10
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