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J Virol
1990 Dec 01;6412:6027-39. doi: 10.1128/JVI.64.12.6027-6039.1990.
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Proteins encoded by the bovine papillomavirus E1 open reading frame: expression in heterologous systems and in virally transformed cells.
Santucci S
,
Androphy EJ
,
Bonne-Andréa C
,
Clertant P
.
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The E1 open reading frame (ORF) of bovine papillomavirus type 1 is required for the persistence of viral genomes as multicopy plasmid molecules in transformed rodent fibroblasts. E1 has been reported to contain two separate complementation groups (M and R, corresponding to N- and C-terminal domains, respectively) which regulate viral replication. However, E1 behaves as a single gene with respect to cell transformation and viral transcription. We examined the proteins translated from the entire ORF by using three antisera raised against E1 peptide or bacterial fusion proteins. The capacity of the whole ORF to encode a 72-kDa protein was demonstrated by translation of synthetic RNA in a reticulocyte lysate system, by microinjection of RNA into Xenopus oocytes, and by expression in recombinant baculoviruses and vaccinia viruses. In eucaryotic cells, this protein was found to be phosphorylated and targeted to the cell nucleus. In vitro translation also produced shorter peptides, containing only the E1 C-terminal domain, because of internal translation starts on the third and fourth methionine codons within E1 ORF. On the other hand, mammalian cells infected by vaccinia E1 recombinant virus contained additional larger E1 phosphoproteins (transient 85-kDa and stable 88-kDa species), likely representing processed forms of the 72-kDa species. The E1 72-kDa nuclear phosphoprotein was detected in bovine papillomavirus type 1-transformed cells. We report the biochemical characteristics of full-sized and truncated E1 proteins: (i) the C-terminal half of E1 ORF contains a phosphorylation site(s); (ii) the full-sized E1, but not the C-terminal protein, binds DNA, without indication for recognition of defined sequences, and critical determinants for this activity are likely confined to an N-terminal domain of the protein; (iii) covalent affinity labeling experiments performed on vaccinia virus-encoded E1 proteins with an ATP analog confirmed our previous observation of sequence similarities between the E1 C-terminal domain and the ATPase domain of simian virus 40 large T antigen.
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