Transformation by the human adenoviruses

Oncogenic transformation by the human adenoviruses involves the concerted action of two genes, E1A and E1B. Over the last few years the products of these genes have been characterised in considerable detail using genetic, immunological and biochemical means. The E1A gene by itself can immortalise primary cells and can cooperate to effect full morphological transformation not only with E1B but also with other known oncogenes. The immortalisation and cooperation activities of E1A require multiple functions that are directed by structurally and functionally independent regions of the E1A protein. These regions coincide with sites of protein: protein interaction between E1A and a variety of cellular polypeptides. One of these, the Rb protein, is a known regulator of the mammalian cell cycle. The E1B region encodes two proteins required for transformation, the larger of which binds to the p53 cellular protein. This protein has also been implicated as a negative regulator of cell growth. It appears therefore that E1A and E1B carry out their many functions associated with transformation at least in part by binding to and presumably modulating the activity of key cellular regulators.