Deregulation of cell cycle progression is a fundamental feature of a number of human diseases, including cancer. In the mamalian pathway, the retinoblastoma protein (pRb) acts as a key regulator of the late G1 restriction point, where fundamental decisions are taken whether a cell should proliferate, differentiate, or undergo apoptosis. Critical for pRb's ability to regulate cell proliferation is the binding to and inhibition of certain members of the E2F transcription factor family (E2F-1 to -3). The physiological function of the two pRb-homologs, plO7 and pl30 is not known, and they have not been found altered in any human cancer so far. p 107 and p 130 associate with and inhibit the activity of two other members of the E2F family (E2F-4 and -5).
In this project, I propose to investigate what domains of the E2F proteins are important for their biological and biochemical function. Once important domains have been delineated, the physiological function of the domains will be evaluated, and protein(s) interacting with the domains will be identified and the cDNAs cloned.