Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth

doi:10.1038/s42255-021-00524-2

	Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth
	Zhao, Jiang-Sha 1,2,3; Shi, Shuo4 ; Qu, Hai-Yan 1,2; Keckesova, Zuzana 5; Cao, Zi-Jian 2; Yang, Li-Xian 2; Yu, Xiaofu 6; Feng, Limin 1,2; Shi, Zhong 7; Krakowiak, Joanna 8; Mao, Ruo-Ying 1,2; Shen, Yi-Tong 2; Fan, Yu-Meng 2; Fu, Tian-Min 9; Ye, Cunqi 10; Xu, Daqian 1,2,3; Gao, Xiaofei 11; You, Jia 11; Li, Wenbo 8,12; Liang, Tingbo 1,2,3; Lu, Zhimin 1,2,3; Feng, Yu-Xiong 1,2,3
	2022-02-01
发表期刊	NATURE METABOLISM (IF:18.9[JCR-2023],21.0[5-Year])
EISSN	2522-5812
发表状态	已发表
DOI	10.1038/s42255-021-00524-2
摘要	["Tumors can reprogram the functions of metabolic enzymes to fuel malignant growth; however, beyond their conventional functions, key metabolic enzymes have not been found to directly govern cell mitosis. Here, we report that glutamine synthetase (GS) promotes cell proliferation by licensing mitotic progression independently of its metabolic function. GS depletion, but not impairment of its enzymatic activity, results in mitotic arrest and multinucleation across multiple lung and liver cancer cell lines, patient-derived organoids and xenografted tumors. Mechanistically, GS directly interacts with the nuclear pore protein NUP88 to prevent its binding to CDC20. Such interaction licenses activation of the CDC20-mediated anaphase-promoting complex or cyclosome to ensure proper metaphase-to-anaphase transition. In addition, GS is overexpressed in human non-small cell lung cancer and its depletion reduces tumor growth in mice and increases the efficacy of microtubule-targeted chemotherapy. Our findings highlight a moonlighting function of GS in governing mitosis and illustrate how an essential metabolic enzyme promotes cell proliferation and tumor development, beyond its main metabolic function.","Zhao et al. report a role for glutamine synthetase in regulating cell proliferation that does not require the catalytic activity of the enzyme."]
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收录类别	SCI ; SCIE
语种	英语
资助项目	Ministry of Science and Technology of the People's Republic of China[2020YFA0803300] ; National Natural Science Foundation of China[31871369,32011530396,82188102] ; Zhejiang Provincial Natural Science Foundation of China[LD19H160002] ; Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang[2019R01001] ; Czech Science Foundation[18-24473Y]
WOS研究方向	Endocrinology & Metabolism
WOS类目	Endocrinology & Metabolism
WOS记录号	WOS:000753764600001
出版者	NATURE PORTFOLIO
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/159560
专题	免疫化学研究所_特聘教授组_干细胞生物学实验室
通讯作者	Zhao, Jiang-Sha; Liang, Tingbo; Lu, Zhimin; Feng, Yu-Xiong
作者单位	1.Zhejiang Univ, Sch Med, Affiliated Hosp 1, Zhejiang Prov Key Lab Pancreat Dis, Hangzhou, Peoples R China 2.Zhejiang Univ, Sch Med, Inst Translat Med, Hangzhou, Peoples R China 3.Zhejiang Univ, Canc Ctr, Hangzhou, Peoples R China 4.ShanghaiTech Univ, Shanghai Adv Inst Immunochem Studies, Shanghai, Peoples R China 5.Czech Acad Sci, Inst Organ Chem & Biochem, Prague, Czech Republic 6.Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp,Inst Canc & Basic Med,Dept Thorac Radio, Hangzhou, Peoples R China 7.Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp,Dept Med Oncol,Inst Canc & Basic Med, Hangzhou, Peoples R China 8.Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Biochem & Mol Biol, Houston, TX 77030 USA 9.Ohio State Univ, Coll Med, Dept Biol Chem & Pharmacol, Columbus, OH 43210 USA 10.Zhejiang Univ, Life Sci Inst, Hangzhou, Peoples R China 11.Westlake Univ, Sch Life Sci, Hangzhou, Peoples R China 12.Univ Texas Houston, MD Anderson Canc Ctr UTHlth Grad Sch Biomed Sci, Houston, TX USA
推荐引用方式 GB/T 7714	Zhao, Jiang-Sha,Shi, Shuo,Qu, Hai-Yan,et al. Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth[J]. NATURE METABOLISM,2022.
APA	Zhao, Jiang-Sha.,Shi, Shuo.,Qu, Hai-Yan.,Keckesova, Zuzana.,Cao, Zi-Jian.,...&Feng, Yu-Xiong.(2022).Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth.NATURE METABOLISM.
MLA	Zhao, Jiang-Sha,et al."Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth".NATURE METABOLISM (2022).