Toxoplasma gondiiUBL-UBA shuttle proteins contribute to the degradation of ubiquitinylated proteins and are important for synchronous cell division and virulence
Toxoplasma gondiiUBL-UBA shuttle proteins contribute to the degradation of ubiquitinylated proteins and are important for synchronous cell division and virulence
复制标题
弓形虫UBL-UBA穿梭蛋白有助于泛素化蛋白的降解，对于同步细胞分裂和毒力很重要
DOI：
10.1096/fj.202000759rr
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发表时间：
2020-08-17
期刊：
影响因子：
4.8
通讯作者：
Liu, Qun
中科院分区：
文献类型：
--
作者：
Zhang, Heng;Liu, Jing;Liu, Qun
弓形虫是一种专性细胞内顶复门寄生虫，可在免疫功能低下的患者中引起致命疾病。泛素蛋白酶体系统 (UPS) 通过降解泛素化蛋白质来调节许多细胞过程。 UBL-UBA 穿梭蛋白家族将泛素化蛋白护送至蛋白酶体进行降解，是 UPS 的重要组成部分。在这里，我们鉴定了位于弓形虫细胞质和细胞核中的三种 UBL-UBA 穿梭蛋白（TGGT1_304680，DNA 损伤诱导蛋白 1，DDI1；TGGT1_295340，UV 切除修复蛋白 rad23 蛋白，RAD23；和 TGGT1_223680，泛素家族蛋白，DSK2）。穿梭蛋白的缺失抑制了寄生虫的生长并导致泛素化蛋白的积累。三基因敲除菌株的细胞分裂是异步的。此外，我们发现非经典穿梭蛋白DDI1的逆转录病毒天冬氨酸蛋白酶活性对于弓形虫小鼠的毒力很重要。这些结果表明UBL-UBA穿梭蛋白在调节泛素化蛋白的降解和弓形虫细胞分裂中的关键作用。
Toxoplasma gondiiis an obligate intracellular apicomplexan parasite that causes lethal diseases in immunocompromised patients. Ubiquitin-proteasome system (UPS) regulates many cellular processes by degrading ubiquitinylated proteins. The UBL-UBA shuttle protein family, which escorts the ubiquitinylated proteins to the proteasome for degradation, are crucial components of UPS. Here, we identified three UBL-UBA shuttle proteins (TGGT1_304680, DNA damage inducible protein 1, DDI1; TGGT1_295340, UV excision repair protein rad23 protein, RAD23; and TGGT1_223680, ubiquitin family protein, DSK2) localized in the cytoplasm and nucleus ofT gondii. Deletion of shuttle proteins inhibited parasites growth and resulted in accumulation of ubiquitinylated proteins. Cell division of triple-gene knockout strain was asynchronous. In addition, we found that the retroviral aspartic protease activity of the nonclassical shuttle protein DDI1 was important for the virulence ofToxoplasmain mice. These results showed the critical roles of UBL-UBA shuttle proteins in regulating the degradation of ubiquitinylated proteins and cell division ofT gondii.