Phosphoglycerate Kinase 1 Phosphorylates Beclin1 to Induce Autophagy

被引：326

作者：

Qian, Xu ^{[1
,2
]}

Li, Xinjian ^{[1
,2
]}

Cai, Qingsong ^{[1
,2
]}

Zhang, Chuanbao ^{[3
]}

Yu, Qiujing ^{[4
]}

Jiang, Yuhui ^{[1
,2
,4
]}

Lee, Jong-Ho ^{[1
,2
]}

Hawke, David ^{[5
]}

Wang, Yugang ^{[1
,2
]}

Xia, Yan ^{[1
,2
,4
]}

Zheng, Yanhua ^{[1
,2
,4
]}

Jiang, Bing-Hua ^{[6
]}

Liu, David X. ^{[7
]}

Jiang, Tao ^{[3
]}

Lu, Zhimin ^{[1
,2
,8
,9
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Brain Tumor Ctr, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA

[3] Capital Med Univ, Beijing Neurosurg Inst, Beijing 100050, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Inst Cell Metab & Dis,Shanghai Key Lab Pancreat C, Shanghai 200080, Peoples R China

[5] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[6] Nanjing Med Univ, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, State Key Lab Reprod Med, Canc Ctr,Dept Pathol, Nanjing 210029, Jiangsu, Peoples R China

[7] Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Spokane, WA 99202 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[9] Univ Texas Grad Sch Biomed Sci Houston, Houston, TX 77030 USA

来源：

MOLECULAR CELL | 2017年 / 65卷 / 05期

基金：

中国国家自然科学基金;

关键词：

PHOSPHATIDYLINOSITOL 3-KINASE COMPLEXES; SIGNALING PATHWAY; PROTEIN-KINASE; BETA-CATENIN; NUCLEOTIDE SYNTHESIS; BREAST-CANCER; TUMOR-CELLS; METABOLISM; GROWTH; TUMORIGENESIS;

D O I：

10.1016/j.molcel.2017.01.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Autophagy is crucial for maintaining cell homeostasis. However, the precise mechanism underlying autophagy initiation remains to be defined. Here, we demonstrate that glutamine deprivation and hypoxia result in inhibition of mTOR-mediated acetyl-transferase ARD1 S228 phosphorylation, leading to ARD1-dependent phosphoglycerate kinase 1 (PGK1) K388 acetylation and subsequent PGK1-mediated Beclin1 S30 phosphorylation. This phosphorylation enhances ATG14L-associated class III phosphatidylinositol 3-kinase VPS34 activity by increasing the binding of phosphatidylinositol to VPS34. ARD1-dependent PGK1 acetylation and PGK1-mediated Beclin1 S30 phosphorylation are required for glutamine deprivation-and hypoxia-induced autophagy and brain tumorigenesis. Furthermore, PGK1 K388 acetylation levels correlate with Beclin1 S30 phosphorylation levels and poor prognosis in glioblastoma patients. Our study unearths an important mechanism underlying cellular-stress-induced autophagy initiation in which the protein kinase activity of the metabolic enzyme PGK1 plays an instrumental role and reveals the significance of the mutual regulation of autophagy and cell metabolism in maintaining cell homeostasis.

引用

页码：917 / +

页数：21

共 51 条

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