This Article Full Text (PDF) Other Versions of this Article: JVI.02713-07v1 82/9/4511    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Seifried, L. A. Articles by Dick, F. A. Search for Related Content PubMed PubMed Citation Articles by Seifried, L. A. Articles by Dick, F. A.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.02713-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

pRB-E2F1 Complexes are Resistant to Adenovirus E1A-Mediated Disruption

London Regional Cancer Program; Children's Health Research Institute; Departments of Biochemistry, and Microbiology & Immunology, University of Western Ontario, London, Ontario, Canada

^* To whom correspondence should be addressed. Email: fdick{at}uwo.ca.

	Abstract

Disruption of pRB-E2F interactions by E1A is a key event in the adenoviral life cycle that drives expression of early viral transcription and induces cell cycle progression. This function of E1A is complicated by E2F1, an E2F family member that controls multiple processes besides proliferation, including apoptosis and DNA repair. Recently, a second interaction site in pRB that only contacts E2F1 has been discovered, allowing pRB to control proliferation separately from other E2F1 dependent activities. Based on this new insight into pRB-E2F1 regulation, we investigated how E1A affects control of E2F1 by pRB. Our data reveals that pRB-E2F1 interactions are resistant to E1A mediated disruption. Using mutant forms of pRB that selectively force E2F1 to bind through only one of the two binding sites on pRB, we determined that E1A is unable to disrupt E2F1's unique interaction with pRB. Furthermore, analysis of pRB-E2F complexes during adenoviral infection reveals the selective maintenance of pRB-E2F1 interactions despite the presence of E1A. Our experiments also demonstrate that E2F1 functions to maintain cell viability in response to E1A expression. This suggests that adenovirus E1A's seemingly complex mechanism of disrupting pRB-E2F interactions provides selectivity in promoting viral transcription and cell cycle advancement, while maintaining cell viability.