Adenovirus E4orf6 assembles with Cullin5-ElonginB-ElonginC E3 ubiquitin ligase through an HIV/SIV Vif-like BC-box to regulate p53 Kun Luo * ,† , Elana Ehrlich * , Zuoxiang Xiao * ,† , Wenyan Zhang * , Gary Ketner * and Xiao-Fang Yu * ,† ,1 * Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; and † Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China 1 Correspondence: Department of Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, USA. E-mail: xfyu@jhsph.edu The adenovirus protein E4orf6 targets p53 for polyubiquitination and proteasomal degradation and is known to form a complex with the Cul5-ElonginB-ElonginC E3 ubiquitin ligase. However, whether Cul5 is directly responsible for the E4orf6-mediated degradation of p53 remains unclear. By using a dominant-negative mutant of Cul5 and silencing Cul5 expression through RNA interference, we have now demonstrated that E4orf6-mediated p53 degradation requires Cul5. Furthermore, we have identified a lentiviral Vif-like BC-box motif in E4orf6 that is highly conserved among adenoviruses from multiple species. More importantly, we have shown that this Vif-like BC-box is essential for the recruitment of Cul5-ElonginB-ElonginC E3 ubiquitin ligase by E4orf6 and is also required for E4orf6-mediated p53 degradation. E4orf6 selectively recruited Cul5 despite the lack of either a Cul5-box, which is used by cellular substrate receptors to recruit Cul5, or a newly identified HCCH zinc-binding motif, which is used by primate lentiviral Vif to recruit Cul5. Therefore, adenovirus E4orf6 molecules represent a novel family of viral BC-box proteins the cellular ancestor of which is as yet unknown. —Luo, K., Ehrlich, E., Xiao, Z., Zhang, W., Ketner, G., Yu, X.-F. Adenovirus E4orf6 assembles with Cullin5-ElonginB-ElonginC E3 ubiquitin ligase through an HIV/SIV Vif-like BC-box to regulate p53. Key Words: proteasomal degradation • substrate receptor • virology
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Adenovirus E4orf6 assembles with Cullin5-ElonginB-ElonginC E3 ubiquitin ligase through an HIV/SIV Vif-like BC-box to regulate p53
Luo, Kun; Ehrlich, Elana; Xiao, Zuoxiang; Zhang, Wenyan; Ketner, Gary; Yu, Xiao-Fang
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, Volume 21 (8): 1742
Fed of American Socs for Experimental Biology – Jun 1, 2007
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