National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Int J Mol Sci. 2021 Jul 26;22(15):7943. doi: 10.3390/ijms22157943.
() is an important human and veterinary pathogen causing life-threatening disease in immunocompromised patients. The UBL-UBA shuttle protein family are important components of the ubiquitin-proteasome system. Here, we identified a novel UBL-UBA shuttle protein DSK2b that is charactered by an N-terminal ubiquitin-like domain (UBL) and a C-terminal ubiquitin-associated domain (UBA). DSK2b was localized in the cytoplasm and nucleus. The deletion of did not affect the degradation of ubiquitinated proteins, parasite growth in vitro or virulence in mice. The double-gene knockout of and its paralogs (ΔΔ) results in a significant accumulation of ubiquitinated proteins and the asynchronous division of . The growth of ΔΔ was significantly inhibited in vitro, while virulence in mice was not attenuated. In addition, autophagy occurred in the ΔΔ which was speculated to degrade the accumulated ubiquitinated proteins in the parasites. Overall, DSK2b is a novel UBL-UBA shuttle protein contributing to the degradation of ubiquitinated proteins and is important for the synchronous cell division of
疟原虫是一种重要的人兽共患病原体，可导致免疫功能低下患者发生危及生命的疾病。UBL-UBA 穿梭蛋白家族是泛素蛋白酶体系统的重要组成部分。本研究鉴定了一种新型 UBL-UBA 穿梭蛋白 DSK2b，其特征为 N 端泛素样结构域（UBL）和 C 端泛素相关结构域（UBA）。DSK2b 定位于细胞质和细胞核中。缺失不会影响泛素化蛋白的降解、寄生虫在体外的生长或在小鼠中的毒力。 和其同源物 的双基因敲除（ΔΔ）导致泛素化蛋白的大量积累和 的异步分裂。ΔΔ 在体外的生长受到显著抑制，而在小鼠中的毒力并未减弱。此外，ΔΔ 中发生了自噬，推测其可降解寄生虫中积累的泛素化蛋白。总之，DSK2b 是一种新型的 UBL-UBA 穿梭蛋白，有助于泛素化蛋白的降解，对 的同步细胞分裂很重要。
