
<ArticleTitle>Overexpression of simian virus 40 small-T antigen blocks centrosome function and mitotic progression in human fibroblasts.</ArticleTitle>
<AbstractText>Recombinant adenoviruses that express high levels of the simian virus 40 (SV40) <prot>small-t</prot> (<prot>ST</prot>) antigen have been used to study the requirement for <prot>ST</prot> to drive cell cycle proliferation of confluent human diploid fibroblasts. This occurs when either <prot>large-T</prot> (<prot>LT</prot>) antigen or serum is added to provide a second signal. While cells readily completed S phase in these experiments, they were found to accumulate with 4N DNA content. Cellular and nuclear morphology, as well as the biochemical status of cyclin B complexes, showed that these cells entered mitosis but were blocked prior to mitotic metaphase. The defect appears to reflect an inability of cells overexpressing <prot>ST</prot> to form organized centrosomes that duplicate and separate normally during the cell cycle and, therefore, the absence of a mitotic spindle. The ability of <prot>ST</prot> to bind protein <prot>phosphatase 2A</prot> was required for this pattern, suggesting that altered phosphorylation of key centrosomal components may occur when <prot>ST</prot> is overexpressed. Although the possible significance of <prot>ST</prot> effects on the centrosome cycle is not fully understood, these findings suggest that <prot>ST</prot> could influence chromosomal instability patterns that are a hallmark of SV40-transformed cells and <prot>LT</prot> expression.</AbstractText>
