HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.06-7241comv1 21/8/1742    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Luo, K. Articles by Yu, X.-F. Search for Related Content PubMed PubMed Citation Articles by Luo, K. Articles by Yu, X.-F.

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

¹Correspondence: Department of Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, USA. E-mail: xfyu{at}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

This article has been cited by other articles:

				R. A. Schwartz, S. S. Lakdawala, H. D. Eshleman, M. R. Russell, C. T. Carson, and M. D. Weitzman Distinct Requirements of Adenovirus E1b55K Protein for Degradation of Cellular Substrates J. Virol., September 15, 2008; 82(18): 9043 - 9055. [Abstract] [Full Text] [PDF]

				B. J. Stanley, E. S. Ehrlich, L. Short, Y. Yu, Z. Xiao, X.-F. Yu, and Y. Xiong Structural Insight into the Human Immunodeficiency Virus Vif SOCS Box and Its Role in Human E3 Ubiquitin Ligase Assembly J. Virol., September 1, 2008; 82(17): 8656 - 8663. [Abstract] [Full Text] [PDF]

				N. Mahrour, W. B. Redwine, L. Florens, S. K. Swanson, S. Martin-Brown, W. D. Bradford, K. Staehling-Hampton, M. P. Washburn, R. C. Conaway, and J. W. Conaway Characterization of Cullin-box Sequences That Direct Recruitment of Cul2-Rbx1 and Cul5-Rbx2 Modules to Elongin BC-based Ubiquitin Ligases J. Biol. Chem., March 21, 2008; 283(12): 8005 - 8013. [Abstract] [Full Text] [PDF]