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 |
DOI | 10.1016/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-+. |
入库方式: OAI收割
来源:大连化学物理研究所
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