机构：[1]Brain Tumor Center, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[2]Program in Cancer and Stem Cell Biology, Centre for Computational Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore[3]Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Institute of Enzyme Engineering and Medical Diagnosis, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China[4]People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China[5]Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[6]Qingdao University Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao 266061, China[7]State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China其他部门华南肿瘤学国家重点实验室中山大学肿瘤防治中心[8]Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China研究所北京市神经外科研究所首都医科大学附属天坛医院[9]Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[10]Graduate School of Biomedical Sciences, Houston, TX 77030, USA
Overcoming metabolic stress is a critical step in tumor growth. Acetyl coenzyme A (acetyl-CoA) generated from glucose and acetate uptake is important for histone acetylation and gene expression. However, how acetyl-CoA is produced under nutritional stress is unclear. We demonstrate here that glucose deprivation results in AMP-activated protein kinase(AMPK)-mediated acetyl-CoA synthetase 2 (ACSS2) phosphorylation at S659, which exposed the nuclear localization signal of ACSS2 for importin alpha 5 binding and nuclear translocation. In the nucleus, ACSS2 binds to transcription factor EB and translocates to lysosomal and autophagy gene promoter regions, where ACSS2 incorporates acetate generated from histone acetylation turnover to locally produce acetyl-CoA for histone H3 acetylation in these regions and promote lysosomal biogenesis, autophagy, cell survival, and brain tumorigenesis. In addition, ACSS2 S659 phosphorylation positively correlates with AMPK activity in gliomaspecimens and grades of glioma malignancy. These results underscore the significance of nuclear ACSS2-mediated histone acetylation in maintaining cell homeostasis and tumor development.
基金：
National Cancer Institute [2R01 CA109035, 1R01 CA169603, 1R01 CA204996, R01 NS094615]; National Institute of Neurological Disorders and Stroke [1R01 NS089754]; National Institutes of Health/National Cancer Institute (MD Anderson support grant) [P30CA016672]; National Natural Science Foundation of China [81672872, 81472386]
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外文
被引次数：
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中科院(CAS)分区：
出版当年[2017]版：
大类|1 区生物
小类|1 区生化与分子生物学1 区细胞生物学
最新[2023]版：
大类|1 区生物学
小类|1 区生化与分子生物学1 区细胞生物学
第一作者：
第一作者机构：[1]Brain Tumor Center, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
通讯作者：
通讯机构：[1]Brain Tumor Center, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[9]Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[10]Graduate School of Biomedical Sciences, Houston, TX 77030, USA
推荐引用方式(GB/T 7714)：
Li Xinjian,Yu Willie,Qian Xu,et al.Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy[J].MOLECULAR CELL.2017,66(5):684-+.doi:10.1016/j.molcel.2017.04.026.
APA：
Li, Xinjian,Yu, Willie,Qian, Xu,Xia, Yan,Zheng, Yanhua...&Lu, Zhimin.(2017).Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy.MOLECULAR CELL,66,(5)
MLA：
Li, Xinjian,et al."Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy".MOLECULAR CELL 66..5(2017):684-+
生物