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Toxoplasma gondii AP2XII-2 Contributes to Proper Progression through S-Phase of the Cell Cycle.
mSphere ( IF 4.8 ) Pub Date : 2020-09-16 , DOI: 10.1128/msphere.00542-20
Sandeep Srivastava 1 , Michael W White 2 , William J Sullivan 3, 4
Affiliation  

Toxoplasma gondii is a protozoan parasite that causes lifelong chronic infection that can reactivate in immunocompromised individuals. Upon infection, the replicative stage (tachyzoite) converts into a latent tissue cyst stage (bradyzoite). Like other apicomplexans, T. gondii possesses an extensive lineage of proteins called ApiAP2s that contain DNA-binding domains first characterized in plants. The function of most ApiAP2s is unknown. We previously found that AP2IX-4 is a cell cycle-regulated ApiAP2 expressed only in dividing parasites as a putative transcriptional repressor. In this study, we purified proteins interacting with AP2IX-4, finding it to be a component of the recently characterized microrchidia (MORC) transcriptional repressor complex. We further analyzed AP2XII-2, another cell cycle-regulated factor that associates with AP2IX-4. We monitored parallel expression of AP2IX-4 and AP2XII-2 proteins in tachyzoites, detecting peak expression during S/M phase. Unlike AP2IX-4, which is dispensable in tachyzoites, loss of AP2XII-2 resulted in a slowed tachyzoite growth due to a delay in S-phase progression. We also found that AP2XII-2 depletion increased the frequency of bradyzoite differentiation in vitro. These results suggest that multiple AP2 factors collaborate to ensure proper cell cycle progression and tissue cyst formation in T. gondii.

中文翻译:

弓形虫AP2XII-2通过细胞周期的S期促进正常进程。

弓形虫是一种原生动物寄生虫,可引起终身慢性感染,可在免疫功能低下的个体中重新激活。感染后,复制阶段(速殖子)转变为潜伏的组织囊肿阶段(缓殖子)。像其他apicomplexans,弓形虫拥有称为ApiAP2s的广泛蛋白质家族,其中包含首先在植物中表征的DNA结合结构域。大多数ApiAP2的功能未知。我们先前发现,AP2IX-4是细胞周期调控的ApiAP2,仅在寄生虫中作为假定的转录阻遏物表达。在这项研究中,我们纯化了与AP2IX-4相互作用的蛋白质,发现它是最近表征的微毛虫(MORC)转录阻遏物复合物的组成部分。我们进一步分析了AP2XII-2,这是另一个与AP2IX-4相关的细胞周期调控因子。我们监测了速殖子中AP2IX-4和AP2XII-2蛋白的平行表达,检测了S / M期的峰值表达。与可在速殖子中分配的AP2IX-4不同,由于S相进程的延迟,AP2XII-2的丢失导致速殖子的生长减慢。体外。这些结果表明,多个AP2因子协同作用以确保弓形虫中适当的细胞周期进程和组织囊肿形成。
更新日期:2020-09-16
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