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Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma

文献类型：期刊论文

作者Zhou, Lin-Lin9,10; Zhang, Tao10; Xue, Yun7,8; Yue, Chuan6,10; Pan, Yihui5,9; Wang, Pengyu5; Yang, Teng5,10; Li, Meixia4; Zhou, Hu3,5,9; Ding, Kan4,9
刊名NATURE COMMUNICATIONS
出版日期2023-11-03
卷号14期号:1页码:7069
DOI10.1038/s41467-023-42784-4
文献子类Article
英文摘要Chemo-activation of mitochondrial ClpP exhibits promising anticancer properties. However, we are currently unaware of any studies using selective and potent ClpP activators in lung squamous cell carcinoma. In this work, we report on such an activator, ZK53, which exhibits therapeutic effects on lung squamous cell carcinoma in vivo. The crystal structure of ZK53/ClpP complex reveals a pi-pi stacking effect that is essential for ligand binding selectively to the mitochondrial ClpP. ZK53 features on a simple scaffold, which is distinct from the activators with rigid scaffolds, such as acyldepsipeptides and imipridones. ZK53 treatment causes a decrease of the electron transport chain in a ClpP-dependent manner, which results in declined oxidative phosphorylation and ATP production in lung tumor cells. Mechanistically, ZK53 inhibits the adenoviral early region 2 binding factor targets and activates the ataxia-telangiectasia mutated-mediated DNA damage response, eventually triggering cell cycle arrest. Lastly, ZK53 exhibits therapeutic effects on lung squamous cell carcinoma cells in xenograft and autochthonous mouse models.
WOS关键词ELECTRON-TRANSPORT CHAIN ; DNA-DAMAGE ; ANTICANCER COMPOUNDS ; MITOCHONDRIAL ; TARGET ; PROTEASE ; CRYSTALLOGRAPHY ; IDENTIFICATION ; DYSREGULATION ; NETWORKS
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:001142547600028
源URL[http://119.78.100.183/handle/2S10ELR8/309636]  
专题新药研究国家重点实验室
通讯作者Ji, Hongbin; Yang, Cai-Guang
作者单位1.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200120, Peoples R China
2.Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Media, Analyt Res Ctr Organ & Biol Mol, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;
4.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai 201203, Peoples R China;
5.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China;
6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China;
7.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Hangzhou 310024, Peoples R China;
8.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China;
9.Univ Chinese Acad Sci, Beijing 100049, Peoples R China;
10.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 Zhou, Lin-Lin,Zhang, Tao,Xue, Yun,et al. Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma[J]. NATURE COMMUNICATIONS,2023,14(1):7069.
APA Zhou, Lin-Lin.,Zhang, Tao.,Xue, Yun.,Yue, Chuan.,Pan, Yihui.,...&Yang, Cai-Guang.(2023).Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma.NATURE COMMUNICATIONS,14(1),7069.
MLA Zhou, Lin-Lin,et al."Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma".NATURE COMMUNICATIONS 14.1(2023):7069.

入库方式： OAI收割

来源：上海药物研究所

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