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Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth
文献类型：期刊论文
| 作者 | Lv, L; Li, D; Zhao, D; Lin, RT; Chu, YJ; Zhang, H; Zha, ZY; Liu, Y; Li, Z; Xu, YP |
| 刊名 | MOLECULAR CELL
 |
| 出版日期 | 2011 |
| 卷号 | 42期号:6页码:719-730 |
| 通讯作者 | Lei, QY (reprint author), Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Key Lab Mol Med,Minist Educ, Shanghai 200032, Peoples R China.,qlei@fudan.edu.cn |
| 英文摘要 | Most tumor cells take up more glucose than normal cells but metabolize glucose via glycolysis even in the presence of normal levels of oxygen, a phenomenon known as the Warburg effect. Tumor cells commonly express the embryonic M2 isoform of pyruvate kinase (PKM2) that may contribute to the metabolism shift from oxidative phosphorylation to aerobic glycolysis and tumorigenesis. Here we show that PKM2 is acetylated on lysine 305 and that this acetylation is stimulated by high glucose concentration. PKM2 K305 acetylation decreases PKM2 enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy (CMA). Acetylation increases PKM2 interaction with HSC70, a chaperone for CMA, and association with lysosomes. Ectopic expression of an acetylation mimetic K305Q mutant accumulates glycolytic intermediates and promotes cell proliferation and tumor growth. These results reveal an acetylation regulation of pyruvate kinase and the link between lysine acetylation and CMA. |
| 学科主题 | Biochemistry & Molecular Biology; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 关键词[WOS] | LYSINE ACETYLATION ; LYSOSOMAL PROTEOLYSIS ; ALLOSTERIC REGULATION ; PEPTIDE SEQUENCES ; C-MYC ; METABOLISM ; PROTEIN ; INHIBITION ; PROLIFERATION ; GLYCOLYSIS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000292343600004 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/820]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Lv, L,Li, D,Zhao, D,et al. Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth[J]. MOLECULAR CELL,2011,42(6):719-730. |
| APA | Lv, L.,Li, D.,Zhao, D.,Lin, RT.,Chu, YJ.,...&Lei, QY.(2011).Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth.MOLECULAR CELL,42(6),719-730. |
| MLA | Lv, L,et al."Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth".MOLECULAR CELL 42.6(2011):719-730. |
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