Cellular Proteins that are Targets for Transformation by DNA Tumour Viruses

Small DNA tumour viruses produce proteins that redirect cellular gene expression and growth control. The E1A polypeptides of adenovirus perform the functions of transcriptional activation and cellular transformation. These two functions are carried out by different domains within the E1A protein. The E1A protein associates with several cellular proteins, including the product of the retinoblastoma gene, pRb-1. Mutational analysis correlates transformation with the sites required for binding pRb and two other cellular proteins, p107 and a 300 kDa polypeptide. This correlation suggests that these proteins are targets for E1A-mediated transformation. Transforming proteins from other small DNA tumour viruses interact with pRb, raising the possibility that a common event in viral transformation is the inactivation of proteins that inhibit cellular proliferation. The role of the E1A-associated 60 kDa protein, p60, in transformation is being investigated. In the absence of E1A, p60 binds to the human homologue of the Schizosuccharomyces pombe cdc2 gene product, p34, to form a complex that has kinase activity that oscillates during the cell cycle. Ongoing studies of the effect of adenovirus infection, and specifically E1A expression, on this cellular kinase may provide clues to how E1A overcomes cell cycle controls and transforms cells