Cellular SUMO-specific proteases regulate HAdV-C5 E1B-55K SUMOylation and virus-induced cell transformation.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-27 eCollection Date: 2024-01-01 DOI:10.3389/fcimb.2024.1484241

Wing-Hang Ip, Marie Fiedler, Britta Gornott, Malte Morische, Luca D Bertzbach, Thomas Dobner

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Abstract

Various viral proteins are post-translationally modified by SUMO-conjugation during the human adenovirus (HAdV) replication cycle. This modification leads to diverse consequences for target proteins as it influences their intracellular localization or cell transformation capabilities. SUMOylated HAdV proteins include the multifunctional oncoprotein E1B-55K. Our previous research, along with that of others, has demonstrated a substantial influence of yet another adenoviral oncoprotein, E4orf6, on E1B-55K SUMOylation levels. Protein SUMOylation can be reversed by cellular sentrin/SUMO-specific proteases (SENPs). In this study, we investigated the interaction of E1B-55K with cellular SENPs to understand deSUMOylation activities and their consequences for cell transformation mediated by this adenoviral oncoprotein. We show that E1B-55K interacts with and is deSUMOylated by SENP 1, independently of E4orf6. Consistent with these results, we found that SENP 1 prevents E1A/E1B-dependent focus formation in rodent cells. We anticipate these findings to be the groundwork for future studies on adenovirus-host interactions, the mechanisms that underlie E1B-55K SUMOylation, as well as the role of this major adenoviral oncoprotein in HAdV-mediated cell transformation.

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细胞SUMO特异性蛋白酶调控HAdV-C5 E1B-55K SUMOylation和病毒诱导的细胞转化。

在人类腺病毒（HAdV）的复制周期中，各种病毒蛋白会受到 SUMO 连接的翻译后修饰。这种修饰会影响靶蛋白的胞内定位或细胞转化能力，从而导致不同的后果。SUMOylated HAdV 蛋白包括多功能肿瘤蛋白 E1B-55K。我们之前的研究以及其他研究表明，另一种腺病毒肿瘤蛋白 E4orf6 对 E1B-55K SUMOylation 水平有很大影响。蛋白质的 SUMO 化可以被细胞中的 SENPs 逆转。在本研究中，我们研究了 E1B-55K 与细胞 SENPs 的相互作用，以了解这种腺病毒癌蛋白介导的去 SUMOylation 活性及其对细胞转化的影响。我们发现，E1B-55K 与 SENP 1 相互作用并被 SENP 1 去 SUMOyl 化，与 E4orf6 无关。与这些结果一致，我们发现 SENP 1 能阻止啮齿类动物细胞中 E1A/E1B 依赖性病灶的形成。我们预计这些发现将为今后研究腺病毒与宿主的相互作用、E1B-55K SUMOylation 的机制以及这一主要腺病毒肿瘤蛋白在 HAdV 介导的细胞转化中的作用奠定基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Cellular and Infection Microbiology IMMUNOLOGY-MICROBIOLOGY

CiteScore

7.90

自引率

7.00%

发文量

1817

审稿时长

14 weeks

期刊介绍： Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.