Cross-talk between phosphorylation and SUMOylation regulates transforming activities of an adenoviral oncoprotein
Cross-talk between phosphorylation and SUMOylation regulates transforming activities of an adenoviral oncoprotein
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DOI：
10.1038/onc.2012.187
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发表时间：
2013-03-28
期刊：
影响因子：
8
通讯作者：
Dobner, T.
中科院分区：
文献类型：
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作者：
Wimmer, P.;Blanchette, P.;Dobner, T.
自从发现小泛素相关修饰物（SUMO）的翻译后修饰（PTM）以来，已经描述了许多蛋白质被可逆修饰，导致几种细胞途径的改变。有趣的是，各种病原体都可以进入这种修饰系统，尽管其分子机制和功能后果几乎不为人所知。我们发现腺病毒癌蛋白E1B-55K是SUMO结合系统的底物，与其C-末端磷酸化直接相关。E1B-55 K对肿瘤抑制因子p53/染色质重塑因子Daxx的调节是必不可少的，因此，它在原代哺乳动物细胞中的致癌潜力也是必不可少的。在病毒感染中，E1B-55K PTM是定位于病毒转录/复制位点所必需的。此外，我们确定E2酶Ubc9作为E1B-55K的相互作用伙伴，为细胞靶蛋白的SUMO依赖性调节提供了可能的分子解释。总之，这些结果首次提供了E1B-55K PTM如何被调节并随后促进宿主细胞SUMO化机制的利用的证据。Oncogene（2013）32，1626 - 1637; doi：10.1038/onc.2012.187; 2012年5月21日在线发表
Since the discovery of post-translational modification (PTM) by the small ubiquitin-related modifiers (SUMOs), a multitude of proteins have been described to be reversibly modified, resulting in the alteration of several cellular pathways. Interestingly, various pathogens gain access to this modification system, although the molecular mechanisms and functional consequences are barely understood. We show here that the adenoviral oncoprotein E1B-55K is a substrate of the SUMO conjugation system, which is directly linked to its C-terminal phosphorylation. This regulative connection is indispensable for modulation of the tumor suppressor p53/chromatin-remodeling factor Daxx by E1B-55K and, consequently, its oncogenic potential in primary mammalian cells. In virus infection, E1B-55K PTMs are necessary for localization to viral transcription/replication sites. Furthermore, we identify the E2 enzyme Ubc9 as an interaction partner of E1B-55K, providing a possible molecular explanation for SUMO-dependent modulation of cellular target proteins. In conclusion, these results for the first time provide evidence how E1B-55K PTMs are regulated and subsequently facilitate exploitation of the host cell SUMOylation machinery. Oncogene (2013) 32, 1626-1637; doi:10.1038/onc.2012.187; published online 21 May 2012