中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
alpha-Ketoglutarate-Activated NF-kappa B Signaling Promotes Compensatory Glucose Uptake and Brain Tumor Development

文献类型:期刊论文

作者Wang, Xiongjun5,6,7; Liu, Ruilong5,6; Qu, Xiujuan1; Yu, Hua5,6; Chu, Huiying2; Zhang, Yajuan5,6; Zhu, Wencheng5; Wu, Xueyuan4; Gao, Hong5,6; Tao, Bangbao3
刊名MOLECULAR CELL
出版日期2019-10-03
卷号76期号:1页码:148-+
ISSN号1097-2765
DOI10.1016/j.molcel.2019.07.007
通讯作者Li, Guohui(ghli@dicp.ac.cn) ; Yang, Weiwei(wyang@sibcb.ac.cn)
英文摘要The rapid proliferation of cancer cells and dysregulated vasculature within the tumor leads to limited nutrient accessibility. Cancer cells often rewire their metabolic pathways for adaption to nutrient stress, and the underlying mechanism remains largely unknown. Glutamate dehydrogenase 1 (GDH1) is a key enzyme in glutaminolysis that converts glutamate to alpha-ketoglutarate (alpha-KG). Here, we show that, under low glucose, GDH1 is phosphorylated at serine (S) 384 and interacts with RelA and IKK beta. GDH1-produced alpha-KG directly binds to and activates IKK beta and nuclear factor kappa B (NF-kappa B) signaling, which promotes glucose uptake and tumor cell survival by upregulating GLUT1, thereby accelerating gliomagenesis. In addition, GDH1 S384 phosphorylation correlates with the malignancy and prognosis of human glioblastoma. Our finding reveals a unique role of alpha-KG to directly regulate signal pathway, uncovers a distinct mechanism of metabolite-mediated NF-kappa B activation, and also establishes the critical role of alpha-KG-activated NF-kappa B in brain tumor development.
WOS关键词GLUTAMATE-DEHYDROGENASE ; MOLECULAR-DYNAMICS ; FORCE-FIELD ; EXPRESSION ; PHOSPHORYLATION ; ORGANIZATION ; ACETYLATION ; METABOLISM ; SURVIVAL ; SYSTEM
资助项目Chinese Academy of Sciences[XDB19000000] ; National Natural Science Foundation of China[91857120] ; National Natural Science Foundation of China[31471324] ; National Natural Science Foundation of China[21625302] ; National Natural Science Foundation of China[21573217] ; CAS[JCTD-2018-14] ; CAS ; Thousand Talents Plan-Youth
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:000488956800015
资助机构Chinese Academy of Sciences ; Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; CAS ; CAS ; CAS ; CAS ; Thousand Talents Plan-Youth ; Thousand Talents Plan-Youth ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; CAS ; CAS ; CAS ; CAS ; Thousand Talents Plan-Youth ; Thousand Talents Plan-Youth ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; CAS ; CAS ; CAS ; CAS ; Thousand Talents Plan-Youth ; Thousand Talents Plan-Youth ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; CAS ; CAS ; CAS ; CAS ; Thousand Talents Plan-Youth ; Thousand Talents Plan-Youth
源URL[http://cas-ir.dicp.ac.cn/handle/321008/172411]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Li, Guohui; Yang, Weiwei
作者单位1.China Med Univ, Hosp 1, Dept Med Oncol, Shenyang 110001, Liaoning, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Lab Mol Modeling, Dalian 116023, Peoples R China
3.Shanghai Jiao Tong Univ, XinHua Hosp, Sch Med, Dept Neurosurg, Shanghai 200092, Peoples R China
4.Wenzhou Med Coll, Affiliated Hosp 1, Dept Radiat Oncol, Wenzhou 325000, Zhejiang, Peoples R China
5.Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci,CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol,Innovat Ctr Cell Signalin, Shanghai 200031, Peoples R China
6.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai Key Lab Mol Androl, Shanghai 200031, Peoples R China
7.Guangzhou Univ, Sch Life Sci, Precise Genome Engn Ctr, Guangzhou 510006, Guangdong, Peoples R China
推荐引用方式
GB/T 7714
Wang, Xiongjun,Liu, Ruilong,Qu, Xiujuan,et al. alpha-Ketoglutarate-Activated NF-kappa B Signaling Promotes Compensatory Glucose Uptake and Brain Tumor Development[J]. MOLECULAR CELL,2019,76(1):148-+.
APA Wang, Xiongjun.,Liu, Ruilong.,Qu, Xiujuan.,Yu, Hua.,Chu, Huiying.,...&Yang, Weiwei.(2019).alpha-Ketoglutarate-Activated NF-kappa B Signaling Promotes Compensatory Glucose Uptake and Brain Tumor Development.MOLECULAR CELL,76(1),148-+.
MLA Wang, Xiongjun,et al."alpha-Ketoglutarate-Activated NF-kappa B Signaling Promotes Compensatory Glucose Uptake and Brain Tumor Development".MOLECULAR CELL 76.1(2019):148-+.

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来源:大连化学物理研究所

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