南方科技大学知识苑(SUSTech KC): Glucose-induced CRL4COP1-p53 axis amplifies glycometabolism to drive tumorigenesis

题名	Glucose-induced CRL4COP1-p53 axis amplifies glycometabolism to drive tumorigenesis
作者	Su，Yang1 ; Luo，Yifan1,9 ; Zhang，Peitao 2; Lin，Hong1 ; Pu，Weijie 1 ; Zhang，Hongyun 1 ; Wang，Huifang1 ; Hao，Yi 3; Xiao，Yihang 4; Zhang，Xiaozhe1 ; Wei，Xiayun 1 ; Nie，Siyue1 ; Zhang，Keren 5; Fu，Qiuyu 6; Chen，Hao7 ; Huang，Niu 6; Ren，Yan 8; Wu，Mingxuan 4; Chow，Billy Kwok Chong 9; Chen，Xing 3; Jin，Wenfei1 ; Wang，Fengchao 6; Zhao，Li 2; Rao，Feng1
通讯作者	Wang，Fengchao; Zhao，Li; Rao，Feng
共同第一作者	Su，Yang; Luo，Yifan
发表日期	2023-07-06
DOI	10.1016/j.molcel.2023.06.010
发表期刊	Molecular Cell 影响因子和分区
ISSN	1097-2765
EISSN	1097-4164
卷号	83 期号:13页码:2316-2331.e7
摘要	The diabetes-cancer association remains underexplained. Here, we describe a glucose-signaling axis that reinforces glucose uptake and glycolysis to consolidate the Warburg effect and overcome tumor suppression. Specifically, glucose-dependent CK2 O-GlcNAcylation impedes its phosphorylation of CSN2, a modification required for the deneddylase CSN to sequester Cullin RING ligase 4 (CRL4). Glucose, therefore, elicits CSN-CRL4 dissociation to assemble the CRL4 E3 ligase, which targets p53 to derepress glycolytic enzymes. A genetic or pharmacologic disruption of the O-GlcNAc-CK2-CSN2-CRL4 axis abrogates glucose-induced p53 degradation and cancer cell proliferation. Diet-induced overnutrition upregulates the CRL4-p53 axis to promote PyMT-induced mammary tumorigenesis in wild type but not in mammary-gland-specific p53 knockout mice. These effects of overnutrition are reversed by P28, an investigational peptide inhibitor of COP1-p53 interaction. Thus, glycometabolism self-amplifies via a glucose-induced post-translational modification cascade culminating in CRL4-mediated p53 degradation. Such mutation-independent p53 checkpoint bypass may represent the carcinogenic origin and targetable vulnerability of hyperglycemia-driven cancer.
关键词	CK2 CRL4COP1 CSN Glucose Sensing Glycometabolism Neddylation O-GlcNAcylation Overnutrition-associated Cancer P53 Degradation Ubiquitylation
相关链接	[Scopus记录]
收录类别	SCI
语种	英语
重要成果	NI论文
学校署名	第一 ; 共同第一 ; 通讯
资助项目	Guangdong Science and Technology Department[2022A1515010830] ; National Natural Science Foundation of China[31872798] ; National Natural Science Foundation of China[32122026] ; National Natural Science Foundation of China[32270831] ; National Natural Science Foundation of China[82073052] ; National Natural Science Foundation of China[82273078] ; National Natural Science Foundation of China[91853129] ; Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20220530114010022] ; Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20220530114802006] ; Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20220818095605011] ; Science, Technology and Innovation Commission of Shenzhen Municipality[RCJC20221008092757096]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:001041798300001
出版者	CELL PRESS
ESI学科分类	MOLECULAR BIOLOGY & GENETICS
Scopus记录号	2-s2.0-85164269561
来源库	Scopus
引用统计	被引频次[WOS]：5
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/559854
专题	生命科学学院南方科技大学医学院南方科技大学医学院_人类细胞生物和遗传学系
作者单位	1.School of Life Sciences,Southern University of Science and Technology,Shenzhen,Guangdong,China 2.Department of Thyroid and Neck Oncology,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin's Clinical Research Center for Cancer,Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Tianjin Medical University Cancer Institute and Hospital,Tianjin Medical University,Tianjin,China 3.College of Chemistry and Molecular Engineering,Peking University,Beijing,100871,China 4.School of Science,Westlake University,Westlake Laboratory of Life Sciences and Biomedicine,Institute of Natural Sciences,Westlake Institute for Advanced Study,Hangzhou,Zhejiang,China 5.BGI-Shenzhen,Shenzhen,Beishan Industrial Zone 11th building, Yantian District, Guangdong,518083,China 6.National Institute of Biological Sciences,Tsinghua Institute of Multidisciplinary Biomedical Research,Tsinghua University,Beijing,102206,China 7.Department of Human Cell Biology and Genetics,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,China 8.Experiment Center for Science and Technology,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China 9.School of Biological Sciences,The University of Hong Kong,Pokfulam,Hong Kong
第一作者单位	生命科学学院
通讯作者单位	生命科学学院
第一作者的第一单位	生命科学学院
推荐引用方式 GB/T 7714	Su，Yang,Luo，Yifan,Zhang，Peitao,et al. Glucose-induced CRL4COP1-p53 axis amplifies glycometabolism to drive tumorigenesis[J]. Molecular Cell,2023,83(13):2316-2331.e7.
APA	Su，Yang.,Luo，Yifan.,Zhang，Peitao.,Lin，Hong.,Pu，Weijie.,...&Rao，Feng.(2023).Glucose-induced CRL4COP1-p53 axis amplifies glycometabolism to drive tumorigenesis.Molecular Cell,83(13),2316-2331.e7.
MLA	Su，Yang,et al."Glucose-induced CRL4COP1-p53 axis amplifies glycometabolism to drive tumorigenesis".Molecular Cell 83.13(2023):2316-2331.e7.

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文件名称/大小	文献类型	版本类型	开放类型	使用许可	操作
Glucose-induced CRL4（5806KB）	--	--	限制开放	--