Acetylation at lysine 71 inactivates superoxide dismutase 1 and sensitizes cancer cells to genotoxic agents
文献类型：期刊论文
| 作者 | Lin, Chenchu1,2; Zeng, Hanlin2; Lu, Junyan3; Xie, Zuoquan2 ; Sun, Wenyi2; Luo, Cheng3; Ding, Jian2; Yuan, Shengtao1; Geng, Meiyu2; Huang, Min2
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| 刊名 | ONCOTARGET
 |
| 出版日期 | 2015-08-21 |
| 卷号 | 6期号:24页码:20578-20591 |
| 关键词 | acetylation camptothecin SIRT1 superoxide dismutase oxidative stress |
| ISSN号 | 1949-2553 |
| DOI | 10.18632/oncotarget.3987 |
| 文献子类 | Article |
| 英文摘要 | Cancer cells are characterized by a high dependency on antioxidant enzymes to cope with the elevated rates of reactive oxygen species (ROS). Impairing antioxidant capacity in cancer cells disturbs the ROS homeostasis and exposes cancer cells to massive oxidative stress. In this study, we have discovered that superoxide dismutase 1 (SOD1), a major player in maintaining the cellular redox status, was acetylated at lysine 71. This acetylation, which was primarily deacetylated by Sirtuin 1 (SIRT1), suppressed the enzymatic activity of SOD1 via disrupting its association with copper chaperone for SOD1 (CCS). More importantly, genotoxic agents, such as camptothecin (CPT), induced SOD1 acetylation by disrupting its binding with SIRT1. CPT-induced SOD1 acetylation was stimulated by its provoked ROS, suggesting a positive feedback loop, in which ROS per se impairs the antioxidative defence of cancer cells and reinforces oxidative stress stimulated by anticancer agents. The intrinsic abundance of SOD1 acetylation varied among cancer cells, and high level of SOD1 acetylation was correlated with elevated sensitivity to CPT. Together, our findings gained mechanistic insights into how cytotoxic agents fine tune the intracellular ROS homeostasis to strengthen their anticancer effects, and suggested SOD1 acetylation as a candidate biomarker for predicting response to CPT-based chemotherapy. |
| WOS关键词 | FOXO TRANSCRIPTION FACTORS ; OXYGEN SPECIES ROS ; TUMOR XENOGRAFTS ; DNA-DAMAGE ; DEPENDENT REGULATION ; SIRT1 DEACETYLASE ; OXIDATIVE STRESS ; REDOX REGULATION ; APOPTOSIS ; INDUCTION |
| 资助项目 | National Science and Technology Major Project of the Ministry of Science and Technology of China[2012ZX09301001-007] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2012ZX09301001-004] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2015ZX09101009] ; National Marine "863" project[2013AA092902] ; National Natural Science Foundation[81102461] ; National Natural Science Foundation of China[81202549] ; Pujiang Scholar Program Grant by the Shanghai Metropolitan Government[12PJ1410400] |
| WOS研究方向 | Oncology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000360138200073 |
| 出版者 | IMPACT JOURNALS LLC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276435]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Huang, Min |
| 作者单位 | 1.China Pharmaceut Univ, Natl Nanjing New Drug Screening Ctr, Nanjing, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 200031, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lin, Chenchu,Zeng, Hanlin,Lu, Junyan,et al. Acetylation at lysine 71 inactivates superoxide dismutase 1 and sensitizes cancer cells to genotoxic agents[J]. ONCOTARGET,2015,6(24):20578-20591. |
| APA | Lin, Chenchu.,Zeng, Hanlin.,Lu, Junyan.,Xie, Zuoquan.,Sun, Wenyi.,...&Huang, Min.(2015).Acetylation at lysine 71 inactivates superoxide dismutase 1 and sensitizes cancer cells to genotoxic agents.ONCOTARGET,6(24),20578-20591. |
| MLA | Lin, Chenchu,et al."Acetylation at lysine 71 inactivates superoxide dismutase 1 and sensitizes cancer cells to genotoxic agents".ONCOTARGET 6.24(2015):20578-20591. |
入库方式： OAI收割
来源：上海药物研究所
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