Department of Viral Transformation, Leibniz Institute of Virology (LIV), Hamburg, Germany.
Front Cell Infect Microbiol. 2024 Sep 27;14:1484241. doi: 10.3389/fcimb.2024.1484241. eCollection 2024.
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.
在人类腺病毒（HAdV）复制周期中，各种病毒蛋白通过 SUMO 缀合进行翻译后修饰。这种修饰会对靶蛋白产生多种影响，因为它会影响其细胞内定位或细胞转化能力。SUMO 化的 HAdV 蛋白包括多功能致癌蛋白 E1B-55K。我们之前的研究以及其他人的研究表明，另一种腺病毒致癌蛋白 E4orf6 对 E1B-55K SUMO 化水平有很大影响。蛋白 SUMO 化可以被细胞中的 SENTINEL/SUMO 特异性蛋白酶（SENPs）逆转。在这项研究中，我们研究了 E1B-55K 与细胞 SENPs 的相互作用，以了解这种腺病毒致癌蛋白介导的去 SUMO 化活性及其对细胞转化的影响。我们表明，E1B-55K 与 SENP 1 相互作用并被 SENP 1 去 SUMO 化，这与 E4orf6 无关。与这些结果一致，我们发现 SENP 1 可防止杆状细胞中 E1A/E1B 依赖性焦点形成。我们预计这些发现将为未来研究腺病毒-宿主相互作用、E1B-55K SUMO 化的机制以及这种主要腺病毒致癌蛋白在 HAdV 介导的细胞转化中的作用奠定基础。
