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J Virol
2004 Mar 01;785:2615-9. doi: 10.1128/jvi.78.5.2615-2619.2004.
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Bovine papillomavirus replicative helicase E1 is a target of the ubiquitin ligase APC.
Mechali F
,
Hsu CY
,
Castro A
,
Lorca T
,
Bonne-Andrea C
.
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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.
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