Pyruvate Kinase M2: Regulatory Circuits and Potential for Therapeutic Intervention
Pyruvate Kinase M2: Regulatory Circuits and Potential for Therapeutic Intervention
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DOI：
10.2174/13816128113199990484
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发表时间：
2014-05-01
影响因子：
3.1
通讯作者：
Bamezai, Rameshwar N. K.
中科院分区：
文献类型：
--
作者：
Gupta, Vibhor;Wellen, Kathryn E.;Bamezai, Rameshwar N. K.
癌细胞的特征是能量代谢的重新编程。在过去的十年里，人们对癌症中发生的代谢变化的了解有了极大的提高，人们对癌症治疗的新陈代谢靶向产生了极大的兴趣。丙酮酸激酶同工酶M2(简称：PKM2、M2-PK)在调节葡萄糖代谢、支持细胞增殖中起着关键作用。与其他PK亚型一样，PKM2催化糖酵解的最后一个能量产生步骤，但其独特之处在于其受调控的能力。PKM2在多个细胞水平上受到调控，包括基因表达、选择性剪接和翻译后修饰。此外，PKM2还受关键代谢中间体调节，与二十多种不同的蛋白质相互作用。因此，这种同工酶是糖酵解的重要调节因子，并在最近出现的其他新的作用中发挥作用。最近的证据表明，干预复杂的PKM2调控网络对肿瘤细胞的增殖具有严重的后果，表明该酶有可能成为肿瘤治疗的靶点。
Cancer cells are characterized by reprogramming of energy metabolism. Over the last decade, understanding of the metabolic changes that occur in cancer has increased dramatically, with great interest in targeting metabolism for cancer therapy. Pyruvate kinase isoenzyme type M2 (abbreviations: PKM2, M2-PK) plays a key role in modulating glucose metabolism to support cell proliferation. PKM2, like other PK isoforms, catalyzes the last energy-generating step in glycolysis, but is unique in its capacity to be regulated. PKM2 is regulated at several cellular levels, including gene expression, alternative splicing and post-translational modification. In addition, PKM2 is regulated by key metabolic intermediates and interacts with more than twenty different proteins. Hence, this isoenzyme is an important regulator of glycolysis, and additionally functions in other novel roles that have recently emerged. Recent evidence indicates that intervening with the complex regulatory network of PKM2 has severe consequences on tumor cell proliferation, indicating the potential of this enzyme as a target for tumor therapy.