Schistosoma mansoni polo-like kinases and their function in control of mitosis and parasite reproduction
Schistosoma mansoni polo-like kinases and their function in control of mitosis and parasite reproduction
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DOI：
10.1590/s0001-37652011000200022
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Long, Thavy
中科院分区：
文献类型：
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作者：
Dissous, Colette;Grevelding, Christoph G;Long, Thavy
Polo样蛋白是细胞周期进程和有丝分裂的重要调节因子。它们构成了一个保守的丝氨酸/苏氨酸激酶家族，它们在其催化结构域中高度相关，并含有参与蛋白质相互作用和亚细胞定位的POLO盒。在哺乳动物中，5个Plk(PLK1-5)在中心体动力学、纺锤体形成、S期和G2/M检查点以及DNA损伤反应中发挥着不同的作用。PLK1是有丝分裂的关键正向调节因子，在多种类型的肿瘤中过表达。Plk4是PLK家族中的一个不同成员，在中心粒复制中具有重要的功能。在小鼠体内，Plk1或Plk4的纯合子破坏在胚胎中是致命的。两个PLK成员SmPlk1和SmSak分别与Plk1和Plk4同源，存在于寄生的曼氏血吸虫中。SmPlk1的结构和功能分析表明，SmPlk1在非洲爪哇卵母细胞周期G2/M转换的调控中具有保守功能。抗癌药物BI 2536(最有效和最选择性的Plk1抑制剂)特异性地抑制SmPlk1的催化活性，并诱导血吸虫性腺发生深刻变化，表明SmPlk1在寄生虫配子发生中的作用，并有望成为抗血吸虫病的新的化疗靶点。目前对SmSak在细胞周期调节和血吸虫性腺发育中的作用进行了研究。
Polo-like kinases are important regulators of cell cycle progression and mitosis. They constitute a family of conserved serine/threonine kinases which are highly related in their catalytic domains and contain polo boxes involved in protein-protein interactions and subcellular localization. In mammals, five Plks (Plk 1-5) encompass diverse roles in centrosome dynamics, spindle formation, intra S-phase and G2/M checkpoints and DNA damage response. Plk1 is a key positive regulator of mitosis and is overexpressed in various types of cancers. Plk4 is a divergent member of the Plk family, with essential functions in centriole duplication. Homozygous disruption of Plk1 or Plk4 in mice is lethal in embryos. Two Plk members SmPlk1 and SmSak, homologous to Plk1 and Plk4 respectively, are present in the parasitic platyhelminth Schistosoma mansoni. Structural and functional analyses of SmPlk1 have demonstrated its conserved function in the regulation of cell cycle G2/M transition in Xenopus oocytes. The anti-cancer drug BI 2536 (the most potent and selective Plk1 inhibitor) inhibits specifically the catalytic activity of SmPlk1 and induced profound alterations in schistosome gonads, indicating a role of SmPlk1 in parasite gametogenesis and its potential as a novel chemotherapeutic target against schistosomiasis. Functions of SmSak in cell cycle regulation and schistosome gonad development are currently investigated.