title: Role of E1B55K in E4orf6/E1B55K E3 ligase complexes formed by different human adenovirus serotypes.
abstract: The E4orf6 protein of serotypes representing all human adenovirus species forms Cullin-based E3 ubiquitin ligase complexes that facilitate virus infection by inducing degradation of cellular proteins that impede efficient viral replication. This complex also includes the viral E1B55K product believed to bind and introduce substrates for ubiquitination. Heterogeneity in the composition of these ligases exists, as some serotypes form Cul5-based complexes whereas others utilize Cul2. Significant variations in substrate specificities also exist among serotypes, as some degrade certain substrates very efficiently whereas others induce more modest or little degradation. As E1B55K is believed to function as the substrate acquisition component of the ligase, we undertook studies to compare the ability of representative E1B55K proteins to bind substrates with the efficacy of degradation by their respective E4orf6-based ligases. Interestingly, although efficient degradation in some cases corresponded to the ability of E1B55K to bind to or relocalize substrates, there were several examples of substrates that bound efficiently to E1B55K but were not degraded and others in which substrates were degraded even though binding to E1B55K was low or undetectable. These results suggest that transient interactions with E1B55K may be sufficient for efficient substrate degradation and that binding alone is not sufficient, implying that the orientation of the substrate in the ligase complex is probably crucial. Nevertheless, we found that the substrate specificity of certain E4orf6-based ligases could be altered through the formation of hybrid complexes containing E1B55K from another serotype, thus confirming identification of E1B55K as the substrate acquisition component of the complex.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Chi Ying
authors.initials: CY
authors.lastname: Cheng
authors.forename: Timra
authors.initials: T
authors.lastname: Gilson
authors.forename: Peter
authors.initials: P
authors.lastname: Wimmer
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schreiner
authors.forename: Gary
authors.initials: G
authors.lastname: Ketner
authors.forename: Thomas
authors.initials: T
authors.lastname: Dobner
authors.forename: Philip E
authors.initials: PE
authors.lastname: Branton
authors.forename: Paola
authors.initials: P
authors.lastname: Blanchette
mesh_terms: D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000378:metabolism*; D017504:Adenovirus E4 Proteins / Q000235:genetics / Q000378:metabolism*; D000258:Adenovirus Infections, Human / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000821:virology; D000260:Adenoviruses, Human / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D011485:Protein Binding; D059748:Proteolysis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D017501:Adenovirus E1B Proteins; D017504:Adenovirus E4 Proteins; D044767:Ubiquitin-Protein Ligases
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