| Title | NQO1 Stabilizes p53 in Response to Oncogene-Induced Senescence |
| Authors | Liu, Kaiyu Jin, Bo Wu, Chenglin Yang, Jianming Zhan, Xiangwen Wang, Le Shen, Xiaomeng Chen, Jing Chen, Hao Mao, Zebin |
| Affiliation | Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China. Peking Univ, Hosp 1, Dept Clin Lab, Beijing 100034, Peoples R China. Navy Gen Hosp, Ctr Basic Med Sci, Beijing 100048, Peoples R China. |
| Keywords | NQO1 p53 senescence OXIDOREDUCTASE(1) DT-DIAPHORASE CELLULAR SENESCENCE PROTEASOMAL DEGRADATION HUMAN FIBROBLASTS HETEROCHROMATIN FORMATION TUMOR SUPPRESSION ACTIVATION EXPRESSION CANCER CELLS |
| Issue Date | 2015 |
| Publisher | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES |
| Citation | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES.2015,11,(7),762-771. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/419268 |
| ISSN | 1449-2288 |
| DOI | 10.7150/ijbs.11978 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 第一医院 |
