Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Anaphase-Promoting Complex-Cyclosome
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Animals
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Bovine papillomavirus 1 / enzymology*
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Cell Cycle Proteins / metabolism
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Cell Line
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DNA Helicases / chemistry
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DNA Helicases / genetics
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DNA Helicases / metabolism*
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DNA Replication
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DNA, Viral / biosynthesis
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DNA, Viral / genetics
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Enzyme Stability
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F-Box Proteins
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Humans
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Ubiquitin-Protein Ligase Complexes / antagonists & inhibitors
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Ubiquitin-Protein Ligase Complexes / deficiency
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Ubiquitin-Protein Ligase Complexes / genetics
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Ubiquitin-Protein Ligase Complexes / metabolism*
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Ubiquitin-Protein Ligases / antagonists & inhibitors
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Ubiquitin-Protein Ligases / deficiency
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
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Viral Proteins / chemistry
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Viral Proteins / genetics
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Viral Proteins / metabolism*
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Xenopus Proteins
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Xenopus laevis
Substances
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Cell Cycle Proteins
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DNA, Viral
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DNA-Binding Proteins
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E1 protein, Bovine papillomavirus
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F-Box Proteins
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FBXO5 protein, Xenopus
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FBXO5 protein, human
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Viral Proteins
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Xenopus Proteins
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome
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Ubiquitin-Protein Ligases
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DNA Helicases