Emerging roles of PKM2 in cell metabolism and cancer progression

被引:322
作者
Luo, Weibo [1 ,2 ]
Semenza, Gregg L. [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
机构
[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Vasc Program, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[6] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD 21205 USA
[7] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA
基金
日本科学技术振兴机构; 美国国家卫生研究院;
关键词
PYRUVATE-KINASE M2; HYPOXIA-INDUCIBLE FACTOR-1; NUCLEAR TRANSLOCATION; AEROBIC GLYCOLYSIS; GLUCOSE-METABOLISM; PROTEIN-SYNTHESIS; ISOFORM; GENE; RAT; EXPRESSION;
D O I
10.1016/j.tem.2012.06.010
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Increased conversion of glucose to lactate is a key feature of many cancer cells that promotes rapid growth. Pyruvate kinase M2 (PKM2) expression is increased and facilitates lactate production in cancer cells. Modulation of PKM2 catalytic activity also regulates the synthesis of DNA and lipids that are required for cell proliferation, and of NADPH that is required for redox homeostasis. In addition to its role as a pyruvate kinase, PKM2 also functions as a protein kinase and as a transcriptional coactivator. These biochemical activities are controlled by allosteric regulators and post-translational modifications of PKM2 that include acetylation, oxidation, phosphorylation, prolyl hydroxylation, and sumoylation. Given its pleiotropic effects on cancer biology, PKM2 represents an attractive target for cancer therapy.
引用
收藏
页码:560 / 566
页数:7
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