A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission

A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission
复制标题

不同的细胞周期蛋白/细胞周期蛋白依赖性激酶复合物控制疟原虫在配子发育和传播过程中的非典型复制

DOI:
10.1101/2020.02.14.928432
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发表时间:
2020
期刊:
--
影响因子:
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通讯作者:
Balestra A
Balestra A
中科院分区:
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作者:
Balestra A

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细胞周期转换通常是由与细胞周期蛋白结合的细胞周期蛋白依赖性蛋白激酶(CDK)活性的变化触发的。导致疟疾的寄生虫有一个独特的细胞分裂周期的生命周期,以及一系列不同的CDK和周期蛋白,它们的功能和相互依赖关系知之甚少。我们发现,伯氏疟原虫CDK相关蛋白5(CRK5)是配子体中非典型有丝分裂的关键调节因子,也是蚊子传播所必需的。它使复制前复合体中各组分的典型CDK基序磷酸化,是DNA复制所必需的。我们还提供了间接调节伴随的M期进展的证据。在复制周期中,CRK5与单个疟原虫特异性周期蛋白(SOC2)稳定地相互作用,尽管我们没有证据表明SOC2通过转录、翻译或降解来循环。我们的结果提供了证据,证明在疟原虫雄配子配子过程中,这种独特的细胞周期蛋白/CDK对填补了控制DNA复制和M期进展的多个真核细胞周期蛋白激酶的功能空间。
Cell cycle transitions are generally triggered by variation in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. Malaria-causing parasites have a life cycle with unique cell-division cycles, and a repertoire of divergent CDKs and cyclins of poorly understood function and interdependency. We show thatPlasmodium bergheiCDK-related kinase 5 (CRK5), is a critical regulator of atypical mitosis in the gametogony and is required for mosquito transmission. It phosphorylates canonical CDK motifs of components in the pre-replicative complex and is essential for DNA replication. We also provide evidence for indirect regulation of the concomitant M-phase progression. During a replicative cycle, CRK5 stably interacts with a singlePlasmodium-specific cyclin (SOC2), although we obtained no evidence of SOC2 cycling by transcription, translation or degradation. Our results provide evidence that duringPlasmodiummale gametogony, this unique cyclin/CDK pair fills the functional space of multiple eukaryotic cell-cycle kinases controlling DNA replication and M-phase progression.
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