The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1
文献类型：期刊论文
| 作者 | Gao, Ming ; Qi, Zijuan; Deng, Min; Huang, Hongyang; Xu, Zhijie; Guo, Guijie; Jing, Jiajun; Huang, Xiaofeng; Xu, Ming; Kloeber, Jake A.
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| 刊名 | ONCOGENE
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| 出版日期 | 2022-08-12 |
| 卷号 | 41期号:33页码:4018-4027 |
| 关键词 | HEME OXYGENASE-1 ARSENIC TOXICITY UBIQUITINATION USP7/HAUSP ACTIVATION MECHANISMS CANCER NRF2 P53 |
| ISSN号 | 0950-9232 |
| 英文摘要 | Heme oxygenase-1 (HO-1) is an inducible heme degradation enzyme that plays a cytoprotective role against various oxidative and inflammatory stresses. However, it has also been shown to exert an important role in cancer progression through a variety of mechanisms. Although transcription factors such as Nrf2 are involved in HO-1 regulation, the posttranslational modifications of HO-1 after oxidative insults and the underlying mechanisms remain unexplored. Here, we screened and identified that the deubiquitinase USP7 plays a key role in the control of redox homeostasis through promoting HO-1 deubiquitination and stabilization in hepatocytes. We used low-dose arsenic as a stress model which does not affect the transcriptional level of HO-1, and found that the interaction between USP7 and HO-1 is increased after arsenic exposure, leading to enhanced HO-1 expression and attenuated oxidative damages. Furthermore, HO-1 protein is ubiquitinated at K243 and subjected to degradation under resting conditions; whereas when after arsenic exposure, USP7 itself can be ubiquitinated at K476, thereafter promoting the binding between USP7 and HO-1, finally leading to enhanced HO-1 deubiquitination and protein accumulation. Moreover, depletion of USP7 and HO-1 inhibit liver tumor growth in vivo, and USP7 positively correlates with HO-1 protein level in clinical human hepatocellular carcinoma (HCC) specimens. In summary, our findings reveal a critical role of USP7 as a HO-1 deubiquitinating enzyme in the regulation of oxidative stresses, and suggest that USP7 inhibitor might be a potential therapeutic agent for treating HO-1 overexpressed liver cancers. |
| 源URL | [https://ir.rcees.ac.cn/handle/311016/47630]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 通讯作者 | Han, Jinxiang |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Med Sci, Dept Radiat Oncol, Beijing 100021, Peoples R China 3.Chinese Acad Med Sci, State Key Lab Mol Oncol, Beijing 100021, Peoples R China 4.Shandong First Med Univ, Affiliated Hosp 1, Dept Orthoped Surg, Jinan 250014, Shandong, Peoples R China 5.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Ming,Qi, Zijuan,Deng, Min,et al. The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1[J]. ONCOGENE,2022,41(33):4018-4027. |
| APA | Gao, Ming.,Qi, Zijuan.,Deng, Min.,Huang, Hongyang.,Xu, Zhijie.,...&Han, Jinxiang.(2022).The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1.ONCOGENE,41(33),4018-4027. |
| MLA | Gao, Ming,et al."The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1".ONCOGENE 41.33(2022):4018-4027. |
入库方式： OAI收割
来源：生态环境研究中心
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