K Sajeev T, Joshi Garima, Arya Pooja, Mahajan Vibhuti, Chaturvedi Akanksha, Mishra Ram Kumar
Nups and SUMO Biology Group, Department of Biological Sciences, IISER Bhopal, Bhopal, India.
National Centre for Cell Science, Savitribai Phule Pune University, Pune, India.
Front Cell Dev Biol. 2021 Jul 14;9:681057. doi: 10.3389/fcell.2021.681057. eCollection 2021.
Pathogens pose a continuous challenge for the survival of the host species. In response to the pathogens, the host immune system mounts orchestrated defense responses initiating various mechanisms both at the cellular and molecular levels, including multiple post-translational modifications (PTMs) leading to the initiation of signaling pathways. The network of such pathways results in the recruitment of various innate immune components and cells at the site of infection and activation of the adaptive immune cells, which work in synergy to combat the pathogens. Ubiquitination is one of the most commonly used PTMs. Host cells utilize ubiquitination for both temporal and spatial regulation of immune response pathways. Over the last decade, ubiquitin family proteins, particularly small ubiquitin-related modifiers (SUMO), have been widely implicated in host immune response. SUMOs are ubiquitin-like (Ubl) proteins transiently conjugated to a wide variety of proteins through SUMOylation. SUMOs primarily exert their effect on target proteins by covalently modifying them. However, SUMO also engages in a non-covalent interaction with the SUMO-interacting motif (SIM) in target proteins. Unlike ubiquitination, SUMOylation alters localization, interactions, functions, or stability of target proteins. This review provides an overview of the interplay of SUMOylation and immune signaling and development pathways in general. Additionally, we discuss in detail the regulation exerted by covalent SUMO modifications of target proteins, and SIM mediated non-covalent interactions with several effector proteins. In addition, we provide a comprehensive review of the literature on the importance of the SUMO pathway in the development and maintenance of a robust immune system network of the host. We also summarize how pathogens modulate the host SUMO cycle to sustain infectability. Studies dealing mainly with SUMO pathway proteins in the immune system are still in infancy. We anticipate that the field will see a thorough and more directed analysis of the SUMO pathway in regulating different cells and pathways of the immune system. Our current understanding of the importance of the SUMO pathway in the immune system necessitates an urgent need to synthesize specific inhibitors, bioactive regulatory molecules, as novel therapeutic targets.
病原体对宿主物种的生存构成持续挑战。作为对病原体的响应，宿主免疫系统会启动精心编排的防御反应，在细胞和分子水平上启动各种机制，包括多种导致信号通路激活的翻译后修饰（PTM）。这些通路网络会导致在感染部位募集各种先天免疫成分和细胞，并激活适应性免疫细胞，它们协同作用以对抗病原体。泛素化是最常用的PTM之一。宿主细胞利用泛素化对免疫反应通路进行时间和空间调节。在过去十年中，泛素家族蛋白，特别是小泛素相关修饰物（SUMO），已被广泛认为与宿主免疫反应有关。SUMO是通过SUMO化作用与多种蛋白质瞬时结合的类泛素（Ubl）蛋白。SUMO主要通过共价修饰靶蛋白来发挥其作用。然而，SUMO也会与靶蛋白中的SUMO相互作用基序（SIM）进行非共价相互作用。与泛素化不同，SUMO化会改变靶蛋白的定位、相互作用、功能或稳定性。本综述概述了SUMO化与免疫信号传导及一般发育途径之间的相互作用。此外，我们详细讨论了靶蛋白的共价SUMO修饰以及SIM介导的与几种效应蛋白的非共价相互作用所发挥的调节作用。此外，我们全面回顾了关于SUMO通路在宿主强大免疫系统网络的发育和维持中的重要性的文献。我们还总结了病原体如何调节宿主SUMO循环以维持感染性。主要涉及免疫系统中SUMO通路蛋白的研究仍处于起步阶段。我们预计该领域将对SUMO通路在调节免疫系统的不同细胞和通路方面进行全面且更具针对性的分析。我们目前对SUMO通路在免疫系统中的重要性的理解迫切需要合成特定抑制剂、生物活性调节分子作为新型治疗靶点。
