Pyruvate kinase: Function, regulation and role in cancer.
Pyruvate kinase: Function, regulation and role in cancer.
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DOI：
10.1016/j.semcdb.2015.08.004
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发表时间：
2015-07
影响因子：
7.3
通讯作者：
Vander Heiden MG
中科院分区：
文献类型：
--
作者：
Israelsen WJ;Vander Heiden MG
丙酮酸激酶是一种在糖酵解中催化磷酸烯醇丙酮酸和ADP转化为丙酮酸和ATP的酶，在调节细胞代谢中起作用。有四种哺乳动物丙酮酸激酶同工型具有独特的组织表达模式和调节特性。丙酮酸激酶（PKM 2）的M2亚型支持合成代谢，并在癌症和正常组织中表达。PKM 2的酶活性受细胞内信号传导途径和代谢物的变构调节; PKM 2因此整合信号传导和代谢输入以根据细胞的需要调节葡萄糖代谢。最近的进展增加了我们对丙酮酸激酶代谢调节的理解，提出了新的问题，并建议非经典PKM 2功能通过蛋白质-蛋白质相互作用和蛋白激酶活性调节基因表达和细胞周期进程的可能性。在这里，我们回顾了丙酮酸激酶的结构，功能和调节，并讨论这些特性如何使PKM 2的细胞增殖和肿瘤生长的调节。
Pyruvate kinase is an enzyme that catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP in glycolysis and plays a role in regulating cell metabolism. There are four mammalian pyruvate kinase isoforms with unique tissue expression patterns and regulatory properties. The M2 isoform of pyruvate kinase (PKM2) supports anabolic metabolism and is expressed both in cancer and normal tissue. The enzymatic activity of PKM2 is allosterically regulated by both intracellular signaling pathways and metabolites; PKM2 thus integrates signaling and metabolic inputs to modulate glucose metabolism according to the needs of the cell. Recent advances have increased our understanding of metabolic regulation by pyruvate kinase, raised new questions, and suggested the possibility of non-canonical PKM2 functions to regulate gene expression and cell cycle progression via protein-protein interactions and protein kinase activity. Here we review the structure, function, and regulation of pyruvate kinase and discuss how these properties enable regulation of PKM2 for cell proliferation and tumor growth.