Toxoplasma gondii exploits UHRF1 and induces host cell cycle arrest at G2 to enable its proliferation
Toxoplasma gondii exploits UHRF1 and induces host cell cycle arrest at G2 to enable its proliferation
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DOI：
10.1111/j.1462-5822.2007.01093.x
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发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Mousli, Marc
中科院分区：
文献类型：
--
作者：
Brunet, Julie;Pfaff, Alexander W.;Mousli, Marc
刚地弓形虫是一种专性细胞内寄生虫，可引起人类严重疾病。它能够感染所有有核哺乳动物细胞，导致寄生虫在宿主体内终身持续存在。本文研究了T.弓形虫感染对宿主细胞增殖的影响，并探讨其参与宿主细胞周期进程的分子机制。我们找到了T.在UHRF 1存在下，弓形虫可诱导宿主细胞发生G1/S转换，随后细胞周期蛋白B1表达下调，导致G2期阻滞，这可能是导致G2期阻滞的主要原因。在G2/M检查点的其他分子包括p53、p21和Cdk 1被正常调节。有趣的是，虽然寄生虫增殖在处于G2期的细胞中是正常的，但在由UHRF 1-siRNA诱导的G1停滞细胞中被抑制，这表明通过UHRF 1诱导的G1/S转换的G2期对于T.弓形虫生长
Toxoplasma gondii is an obligate intracellular parasite that causes severe disease in humans. It is able to infect all nucleated mammalian cells leading to lifelong persistence of the parasite in the host. Here, we studied the effect of T. gondii infection on host cell proliferation and explored the molecular mechanisms involved in host cell cycle progression. We found that T. gondii induced G1/S transition in host cells in the presence of UHRF1, followed by G2 arrest after cyclin B1 downregulation which is probably the major cause of the arrest. Other molecules at the G2/M checkpoint including p53, p21 and Cdk1 were normally regulated. Interestingly, while parasite proliferation was normal in cells that were in the G2 phase, it was suppressed in G1-arrested cells induced by UHRF1-siRNA, indicating the importance of the G2 phase via UHRF1-induced G1/S transition for T. gondii growth.