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丙酮酸激酶同工酶M2在控制细胞周期进程和肿瘤发生中的非代谢功能

Nonmetabolic functions of pyruvate kinase isoform M2 in controlling cell cycle progression and tumorigenesis.

作者信息

Lu Zhimin

机构信息

Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Chin J Cancer. 2012 Jan;31(1):5-7. doi: 10.5732/cjc.011.10446. Epub 2011 Dec 23.

DOI:10.5732/cjc.011.10446
PMID:22200182
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3777463/
Abstract

Pyruvate kinase catalyzes the rate-limiting final step of glycolysis, generating adenosine triphosphate (ATP) and pyruvate. The M2 tumor-specific isoform of pyruvate kinase (PKM2) promotes glucose uptake and lactate production in the presence of oxygen, known as aerobic glycolysis or the Warburg effect. As recently reported in Nature, PKM2, besides its metabolic function, has a nonmetabolic function in the direct control of cell cycle progression by activating β-catenin and inducing expression of the β-catenin downstream gene CCND1(encoding for cyclin D1). This nonmetabolic function of PKM2 is essential for epidermal growth factor receptor (EGFR) activation-induced tumorigenesis.

摘要

丙酮酸激酶催化糖酵解的限速终末步骤，生成三磷酸腺苷（ATP）和丙酮酸。丙酮酸激酶的M2肿瘤特异性同工型（PKM2）在有氧条件下促进葡萄糖摄取和乳酸生成，这一现象被称为有氧糖酵解或瓦伯格效应。正如最近发表在《自然》杂志上的报道，PKM2除了具有代谢功能外，还通过激活β-连环蛋白并诱导β-连环蛋白下游基因CCND1（编码细胞周期蛋白D1）的表达，在直接控制细胞周期进程方面具有非代谢功能。PKM2的这种非代谢功能对于表皮生长因子受体（EGFR）激活诱导的肿瘤发生至关重要。

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本文引用的文献

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Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation.核 PKM2 在 EGFR 激活时调节β-连环蛋白的转录激活。
Nature. 2011 Dec 1;480(7375):118-22. doi: 10.1038/nature10598.
2
Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses.活性氧抑制丙酮酸激酶 M2 有助于细胞抗氧化反应。
Science. 2011 Dec 2;334(6060):1278-83. doi: 10.1126/science.1211485. Epub 2011 Nov 3.
3
Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1.丙酮酸激酶 M2 是一种受 PHF3 刺激的缺氧诱导因子 1 共激活剂。
Cell. 2011 May 27;145(5):732-44. doi: 10.1016/j.cell.2011.03.054.
4
EGF-induced ERK activation promotes CK2-mediated disassociation of alpha-Catenin from beta-Catenin and transactivation of beta-Catenin.表皮生长因子（EGF）诱导的细胞外信号调节激酶（ERK）激活促进酪蛋白激酶2（CK2）介导的α-连环蛋白与β-连环蛋白解离以及β-连环蛋白的反式激活。
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Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth.酪氨酸磷酸化抑制 PKM2 以促进瓦博格效应和肿瘤生长。
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Science. 2009 May 22;324(5930):1029-33. doi: 10.1126/science.1160809.
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Wnt/beta-catenin signaling: new (and old) players and new insights.Wnt/β-连环蛋白信号传导：新（及旧）参与者与新见解
Curr Opin Cell Biol. 2008 Apr;20(2):119-25. doi: 10.1016/j.ceb.2008.01.009. Epub 2008 Mar 12.
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The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth.丙酮酸激酶的M2剪接异构体对癌症代谢和肿瘤生长很重要。
Nature. 2008 Mar 13;452(7184):230-3. doi: 10.1038/nature06734.
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Pyruvate kinase M2 is a phosphotyrosine-binding protein.丙酮酸激酶M2是一种磷酸酪氨酸结合蛋白。
Nature. 2008 Mar 13;452(7184):181-6. doi: 10.1038/nature06667.
10
Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity.AKT对β-连环蛋白的磷酸化作用可促进β-连环蛋白的转录活性。
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