Research Papers:

Acetylation at lysine 71 inactivates superoxide dismutase 1 and sensitizes cancer cells to genotoxic agents

Chenchu Lin, Hanlin Zeng, Junyan Lu, Zuoquan Xie, Wenyi Sun, Cheng Luo, Jian Ding, Shengtao Yuan, Meiyu Geng and Min Huang _

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Oncotarget. 2015; 6:20578-20591. https://doi.org/10.18632/oncotarget.3987

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Chenchu Lin1,2,*, Hanlin Zeng1,*, Junyan Lu3, Zuoquan Xie1, Wenyi Sun1, Cheng Luo3, Jian Ding1, Shengtao Yuan2, Meiyu Geng1 and Min Huang1

1 Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

2 National Nanjing New Drug Screening Center, China Pharmaceutical University, Nanjing, China

3 Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

* These authors have contributed equally to this work

Correspondence to:

Min Huang, email:

Meiyu Geng, email:

Keywords: acetylation, camptothecin, SIRT1, superoxide dismutase, oxidative stress

Received: March 03, 2015 Accepted: April 10, 2015 Published: May 04, 2015


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.

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