THE PRB-RELATED PROTEIN P107 CONTAINS 2 GROWTH SUPPRESSION DOMAINS - INDEPENDENT INTERACTIONS WITH E2F AND CYCLIN CDK COMPLEXES

Unregulated expression of either the retinoblastoma protein (pRB) or t he related protein p107 can cause growth arrest of sensitive cells in the G(1) phase of the cell cycle. However, growth arrests mediated by p107 and pRB are not identical. Through structure - function and co-ex pression analyses we have dissected the p107 molecule into two domains that independently are able to block cell cycle progression. One doma in corresponds to the sequences needed for interaction with the transc ription factor E2F, and the other corresponds to the interaction domai n for cyclin A or cyclin E complexes. In cervical carcinoma cell line C33A, which was previously shown to be sensitive to p107 but resistant to pRB growth suppression, only the cyclin binding domain is active a s a growth suppressor. Furthermore, we show that these two independent domains are functional in untransformed mouse fibroblasts. Together, these results provide experimental evidence for the presence of two fu nctional domains in p107 and pinpoint an important functional differen ce between p107 and pRB.