JVI Accepts, published online ahead of print on 6 August 2008

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J. Virol. doi:10.1128/JVI.01240-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Bap31 is a Novel Target of the Human Papillomavirus E5 Protein

Jennifer A. Regan and Laimonis A. Laimins^*

Department of Microbiology - Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611 USA

^* To whom correspondence should be addressed. Email: l-laimins{at}northwestern.edu.

The E5 proteins of human papillomaviruses (HPV) are small hydrophobic proteins that are expressed in the early and late stages of the viral life cycle, however, their role in HPV pathogenesis is not clearly understood. In this study, a split-ubiquitin yeast two-hybrid system was used to identify B-cell associated protein 31 (Bap31) as a binding partner of HPV E5 proteins. The association of these proteins was confirmed by co-immunoprecipitation of complexes of Bap31 with either HPV 16 or 31 E5. In addition, Bap 31 and E5 were found to co-localize in perinuclear patterns consistent with localization to the endoplasmic reticulum. Mutational analysis of E5 identified amino acids in the extreme C terminus as important for stabilizing the interaction with Bap31. Deletion of these C-terminal amino acids of E5 in the context of complete HPV 31 genomes resulted in impaired proliferative capacity of HPV-positive keratinocytes following differentiation. Using siRNAs to reduce the levels of Bap31, the proliferative ability of HPV–positive keratinocytes upon differentiation was also reduced implicating Bap31 as a regulator of this process. These studies identify a novel binding partner of the high-risk HPV E5 proteins and provide insight into how the E5 proteins may modulate the life cycle in differentiating cells.

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