title: Cross-talk between phosphorylation and SUMOylation regulates transforming activities of an adenoviral oncoprotein.
abstract: 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.
authors.affiliation: Department of Molecular Virology, Heinrich-Pette-Institute-Leibniz-Institute for Experimental Virology, Hamburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Wimmer
authors.forename: P
authors.initials: P
authors.lastname: Blanchette
authors.forename: S
authors.initials: S
authors.lastname: Schreiner
authors.forename: W
authors.initials: W
authors.lastname: Ching
authors.forename: P
authors.initials: P
authors.lastname: Groitl
authors.forename: J
authors.initials: J
authors.lastname: Berscheminski
authors.forename: P E
authors.initials: PE
authors.lastname: Branton
authors.forename: H
authors.initials: H
authors.lastname: Will
authors.forename: T
authors.initials: T
authors.lastname: Dobner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D056970:Co-Repressor Proteins; D057809:HEK293 Cells; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D010802:Phylogeny; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000502:physiology; D051381:Rats; D020239:Receptor Cross-Talk / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D058207:Sumoylation / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C553319:E1B55K protein, adenovirus; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D011494:Protein Kinases