The APC/C and CBP/p300 cooperate to regulate transcription and cell-cycle progression.

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.

T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia.

Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo.

Detection of CD4(+)- and CD8(+)-T-cell responses to human papillomavirus type 1 antigens expressed at various stages of the virus life cycle by using an enzyme-linked immunospot assay of gamma interferon release.

Human papillomavirus (HPV) antigens are expressed in epithelial cells at different stages of differentiation, and this may affect how they are handled by the immune system. We assessed the relative immunogenicities of four different HPV type 1 proteins: E6 and E7, which are made early in basal or parabasal cells; E4, which is made suprabasally in differentiating cells; and L1, a late protein which appears in the highly differentiated upper spinous layers. Pools of 15-mer peptides covering the primary sequences of all four proteins were used to screen 15 normal donors in enzyme-linked immunospot assays of gamma interferon release for both CD4(+)- and CD8(+)-T-cell reactivities.

Definition of a major p53 binding site on Ad2E1B58K protein and a possible nuclear localization signal on the Ad12E1B54K protein.

Previous studies have established that adenovirus 2/5 early region 1B (Ad E1B) 58K protein binds p53 strongly and co-localizes with it to cytoplasmic dense bodies whilst the homologous Ad12E1B54K protein binds only weakly and co-localizes primarily to the nucleus in Ad12E1 transformed cells. We have used these properties of the E1B proteins from different viral serotypes to map the p53 binding site on the Ad2/5 protein. A set of chimaeric genes was constructed containing different proportions of the Ad12 and Ad2E1B DNA.

Adenovirus early region 1A protein binds to mammalian SUG1-a regulatory component of the proteasome.

Adenovirus early region 1A (Ad E1A) is a multifunctional protein which is essential for adenovirus-mediated transformation and oncogenesis. Whilst E1A is generally considered to exert its influence on recipient cells through regulation of transcription it also increases the level of cellular p53 by increasing the protein half-life. With this in view, we have investigated the relationship of Ad E1A to the proteasome, which is normally responsible for degradation of p53.