Parkin Regulates the Activity of Pyruvate Kinase M2.
Parkin Regulates the Activity of Pyruvate Kinase M2.
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DOI：
10.1074/jbc.m115.703066
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发表时间：
2016-05-06
期刊：
影响因子：
--
通讯作者：
Zhao W
中科院分区：
文献类型：
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作者：
Liu K;Li F;Han H;Chen Y;Mao Z;Luo J;Zhao Y;Zheng B;Gu W;Zhao W
Parkin是一种泛素E3连接酶，在大多数常染色体隐性遗传早发性帕金森病病例中发生突变。研究发现，Parkin在胶质母细胞瘤和其他人类恶性肿瘤中也发生突变，并抑制肿瘤细胞生长。在这里，我们确定丙酮酸激酶M2（PKM2）作为一个独特的底物帕金通过生化纯化。我们发现parkin在体外和体内都与PKM2相互作用，并且这种相互作用在葡萄糖饥饿期间显著增加。帕金蛋白对PKM2的泛素化不影响其稳定性，但降低其酶活性。帕金调节糖酵解途径并影响细胞代谢。本研究揭示了parkin在肿瘤细胞代谢中的重要作用，为帕金森病的治疗提供了新的思路。
Parkin, a ubiquitin E3 ligase, is mutated in most cases of autosomal recessive early onset Parkinson disease. It was discovered that Parkin is also mutated in glioblastoma and other human malignancies and that it inhibits tumor cell growth. Here, we identified pyruvate kinase M2 (PKM2) as a unique substrate for parkin through biochemical purification. We found that parkin interacts with PKM2 both in vitro and in vivo, and this interaction dramatically increases during glucose starvation. Ubiquitylation of PKM2 by parkin does not affect its stability but decreases its enzymatic activity. Parkin regulates the glycolysis pathway and affects the cell metabolism. Our studies revealed the novel important roles of parkin in tumor cell metabolism and provided new insight for therapy of Parkinson disease.