Carvalho Teresa Gil, Doerig Christian, Reininger Luc
Department of Microbiology, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
Biochim Biophys Acta. 2013 Jul;1834(7):1336-45. doi: 10.1016/j.bbapap.2013.02.022. Epub 2013 Feb 24.
Completion of the life cycle of malaria parasite requires a succession of developmental stages which vary greatly with respect to proliferation status, implying a tightly regulated control of the parasite's cell cycle, which remains to be understood at the molecular level. Progression of the eukaryotic cell cycle is controlled by members of mitotic kinase of the families CDK (cyclin-dependent kinases), Aurora, Polo and NIMA. Plasmodium parasites possess cyclin-dependent protein kinases and cyclins, which strongly suggests that some of the principles underlying cell cycle control in higher eukaryotes also operate in this organism. However, atypical features of Plasmodium cell cycle organization and important divergences in the composition of the cell cycle machinery suggest the existence of regulatory mechanisms that are at variance with those of higher eukaryotes. This review focuses on several recently described Plasmodium protein kinases related to the NIMA and Aurora kinase families and discusses their functional involvement in parasite's biology. Given their demonstrated essential roles in the erythrocytic asexual cycle and/or sexual stages, these enzymes represent novel potential drug targets for antimalarial intervention aiming at inhibiting parasite replication and/or blocking transmission of the disease. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).
疟原虫生命周期的完成需要一系列发育阶段,这些阶段在增殖状态方面差异很大,这意味着对寄生虫细胞周期有严格调控,而这在分子水平上仍有待理解。真核细胞周期的进程由CDK(细胞周期蛋白依赖性激酶)、极光激酶、波罗蛋白激酶和NIMA等有丝分裂激酶家族的成员控制。疟原虫拥有细胞周期蛋白依赖性蛋白激酶和细胞周期蛋白,这强烈表明高等真核生物中细胞周期控制的一些基本原理在这种生物体中也起作用。然而,疟原虫细胞周期组织的非典型特征以及细胞周期机制组成的重要差异表明存在与高等真核生物不同的调控机制。本综述重点关注了几种最近描述的与NIMA和极光激酶家族相关的疟原虫蛋白激酶,并讨论了它们在寄生虫生物学中的功能作用。鉴于它们在红细胞无性周期和/或有性阶段已证明的重要作用,这些酶代表了抗疟干预的新型潜在药物靶点,旨在抑制寄生虫复制和/或阻断疾病传播。本文是名为《蛋白激酶抑制剂(2012)》特刊的一部分。