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Nucleolar c‐Myc recruitment by a Vibrio T3SS effector promotes host cell proliferation and bacterial virulence
The EMBO Journal ( IF 9.4 ) Pub Date : 2020-12-21 , DOI: 10.15252/embj.2020105699
Maozhi Hu 1 , Yibei Zhang 1 , Dan Gu 1 , Xiang Chen 2 , Matthew K Waldor 2, 3 , Xiaohui Zhou 1
Affiliation  

Pathogen type 3 secretion systems (T3SS) manipulate host cell pathways by directly delivering effector proteins into host cells. In Vibrio parahaemolyticus, the leading cause of bacterial seafood‐borne diarrheal disease, we showed that a T3SS effector, VgpA, localizes to the host cell nucleolus where it binds Epstein–Barr virus nuclear antigen 1‐binding protein 2 (EBP2). An amino acid substitution in VgpA (VgpAL10A) did not alter its translocation to the nucleus but abolished the effector’s capacity to interact with EBP2. VgpA‐EBP2 interaction led to the re‐localization of c‐Myc to the nucleolus and increased cellular rRNA expression and proliferation of cultured cells. The VgpA‐EBP2 interaction elevated EBP2’s affinity for c‐Myc and prolonged the oncoprotein’s half‐life. Studies in infant rabbits demonstrated that VgpA is translocated into intestinal epithelial cells, where it interacts with EBP2 and leads to nucleolar re‐localization of c‐Myc. Moreover, the in vivo VgpA‐EBP2 interaction during infection led to proliferation of intestinal cells and heightened V. parahaemolyticus’ colonization and virulence. These observations suggest that direct effector stimulation of a c‐Myc controlled host cell growth program can contribute to pathogenesis.

中文翻译:


弧菌 T3SS 效应子募集核仁 c-Myc 可促进宿主细胞增殖和细菌毒力



病原体 3 型分泌系统 (T3SS) 通过直接将效应蛋白递送到宿主细胞中来操纵宿主细胞通路。在副溶血性弧菌(细菌性海鲜传播性腹泻病的主要原因)中,我们发现 T3SS 效应子 VgpA 定位于宿主细胞核仁,在此结合 Epstein-Barr 病毒核抗原 1 结合蛋白 2 (EBP2)。 VgpA (VgpA L10A ) 中的氨基酸取代不会改变其向细胞核的易位,但会消除效应子与 EBP2 相互作用的能力。 VgpA-EBP2 相互作用导致 c-Myc 重新定位到核仁,并增加细胞 rRNA 表达和培养细胞的增殖。 VgpA-EBP2 相互作用提高了 EBP2 对 c-Myc 的亲和力并延长了癌蛋白的半衰期。对幼兔的研究表明,VgpA 易位到肠上皮细胞中,与 EBP2 相互作用并导致 c-Myc 的核仁重新定位。此外,感染期间体内VgpA-EBP2相互作用导致肠细胞增殖并增强副溶血性弧菌的定植和毒力。这些观察结果表明,ac-Myc 控制的宿主细胞生长程序的直接效应器刺激可能有助于发病机制。
更新日期:2021-01-15
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