Brunet Julie, Pfaff Alexander W, Abidi Ahmed, Unoki Motoko, Nakamura Yusuke, Guinard Marie, Klein Jean-Paul, Candolfi Ermanno, Mousli Marc
Institut de Parasitologie et de Pathologie Tropicale de Strasbourg, UPRES E.A. 3950 Interactions Cellulaires et Moléculaires Hôte-Parasite, Faculté de Médecine, Université Louis Pasteur, 67000 Strasbourg, France.
Cell Microbiol. 2008 Apr;10(4):908-20. doi: 10.1111/j.1462-5822.2007.01093.x. Epub 2007 Nov 14.
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.
刚地弓形虫是一种专性细胞内寄生虫，可导致人类患上严重疾病。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生持续存在。在此，我们研究了刚地弓形虫感染对宿主细胞增殖的影响，并探讨了宿主细胞周期进程中涉及的分子机制。我们发现，在存在UHRF1的情况下，刚地弓形虫诱导宿主细胞发生G1/S期转换，随后在细胞周期蛋白B1下调后发生G2期阻滞，这可能是阻滞的主要原因。G2/M期检查点的其他分子，包括p53、p21和Cdk1，均受到正常调控。有趣的是，虽然寄生虫在处于G2期的细胞中增殖正常，但在由UHRF1-siRNA诱导的G1期阻滞细胞中其增殖受到抑制，这表明通过UHRF1诱导的G1/S期转换进入G2期对刚地弓形虫的生长很重要。
