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Journal of Virology, March 2004, p. 2615-2619, Vol. 78, No. 5
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.5.2615-2619.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Chiung-Yueh Hsu,
Anna Castro, Thierry Lorca, and Catherine Bonne-Andrea*
Centre de Recherches de Biochimie Macromoléculaire, CNRS FRE 2593, IFR 122, 34 293 Montpellier Cedex 5, France
Received 23 July 2003/ Accepted 11 November 2003
The papillomavirus E1 replicative helicase is essential for replication and maintenance of extrachromosomal viral genomes in infected cells. We previously found that the bovine papillomavirus E1 protein is a substrate of the ubiquitin-dependent proteolytic pathway. Here we show that E1 is targeted for degradation by the anaphase-promoting complex (APC). Inhibition of APC activity by the specific inhibitor Emi1 or point mutations in the D-box and KEN-box motifs of E1 stabilize the protein and increase viral DNA replication in both a cell-free system and in living cells. These findings involve APC as the ubiquitin ligase that controls E1 levels to maintain a constant low copy number of the viral genome during latent infection.
F.M. and C.-Y.H. contributed equally to this work.
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