We are interested in understanding the molecular mechanisms by which an oncogene alters the growth status of human cells. The adenovirus early region 1A (E1A) gene products have been very useful in the search for the cellular processes and the actual proteins involved in growth regulation. The identification of the product of the retinoblastoma- linked gene and cyclin A gene, as members of the set of proteins complexed with E1A indicates the power of E1A-affinity precipitation to isolate cellular growth regulatory proteins. The fact that numerous mutants of E1A exist that are deficient in one or more of the biological activities ascribed to E1A contributes to the ability to experimentally probe the function of each associated cellular protein. This project focuses on a detailed definition of the cell division cycle modulated association of E1A with cellular proteins, and of the biochemical activities of the complexes isolated from cells throughout the cell cycle. As part of the project we will extend the analysis of the E1A- associated protein. p130. We will clone and sequence the gene for p130. Using the cloned gene product we will begin to determine the structural components necessary for its association with E1A. We will also attempt to disrupt the function of p130 and compare the results to experiments in which we disrupt another E1A with these cellular proteins to reveal mechanisms not only of E1A induced oncogenesis but of the normal growth regulatory properties of these proteins.
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