Antibodies prepared against a human papilloma virus‐1 (HPV‐1) E4/beta‐galactosidase fusion protein identified several polypeptides in HPV‐1, but not HPV‐2 or 4, induced papillomas. The major E4 protein, that represented up to 30% of total cellular protein, was a 16/17‐K doublet which was purified by column chromatography and analysed for amino acid content. A peptide derived by chymotryptic digestion was purified by h.p.l.c. and subjected to amino acid sequencing. The unique sequence obtained, Gly‐His‐Pro‐Asp‐Leu‐Ser‐Leu, identified the 16/17‐K doublet as a product of the HPV‐1 E4 gene region. Antibodies to both the E4/beta‐galactosidase fusion protein and the 16/17‐K doublet identified two smaller polypeptides (10/11‐K) which may represent spliced products of E4. We propose that the products of the HPV‐1 E4 gene region are not classical DNA tumor virus early proteins and suggest that they play a role in virus maturation.

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Oncogene (

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The anaphase-promoting complex/cyclosome (APC/C) is a multicomponent E3 ubiquitin ligase that, by targeting protein substrates for 26S proteasome-mediated degradation through ubiquitination, coordinates the temporal progression of eukaryotic cells through mitosis and the subsequent G1 phase of the cell cycle. Other functions of the APC/C are, however, less well defined. Here we show that two APC/C components, APC5 and APC7, interact directly with the coactivators CBP and p300 through protein-protein interaction domains that are evolutionarily conserved in adenovirus E1A. This interaction stimulates intrinsic CBP/p300 acetyltransferase activity and potentiates CBP/p300-dependent transcription. We also show that APC5 and APC7 suppress E1A-mediated transformation in a CBP/p300-dependent manner, indicating that these components of the APC/C may be targeted during cellular transformation. Furthermore, we establish that CBP is required in APC/C function; specifically, gene ablation of CBP by RNA-mediated interference markedly reduces the E3 ubiquitin ligase activity of the APC/C and the progression of cells through mitosis. Taken together, our results define discrete roles for the APC/C-CBP/p300 complexes in growth regulation.