E2F AS AN SV40/ADENOVIRUS TRANSFORMATION TARGET

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SV40 and the human adenoviruses and seemingly unrelated DNA tumor viruses. Each can transform a variety of cultured cell lines and strains, and each is tumorigenic in rodents. SV40 large T antigen (T) and adenovirus E1A protein carry out a significant part of the transforming work of the relevant virus. Both proteins work in transformation, in part, by forming a complex with the retinoblastoma gene product (RB) and related proteins, e.g. p107. Abundant evidence points to the ability of E1A and T to displace the transcription factor, E2F, from its binding domains on the surfaces of RB and p107. Further evidence suggests that T/E1A displacement of E2F, itself a protein which activates certain genes whose products promote exit from G0/G1, may unleash unregulated action of this protein which is suspected of contributing to the growth stimulatory effects of T and E1A. This application focuses on learning more of how E2F functions in the cell cycle, how its interaction with RB is translated into growth controlling events, Whether it has oncogene potential, whether there are multiple E2F species and, if so, why.