pRb and E2f-1 in mouse development and tumorigenesis.

Our understanding of how RB and E2F-1 function has progressed significantly from the model in which RB negatively regulates expression of genes required for S phase by binding to and inhibiting E2F-1. Both RB and E2F-1 have been shown recently to possess additional properties and mechanisms of regulation relevant to developmental and tumorigenic processes. In particular, it is now realised that RB has E2F-independent tumor suppressor functions which rely upon the ability of RB to induce differentiation. For its part, E2F-1 is unique amongst E2F family members in its capacity to induce apoptosis and this function is clearly relevant to our appreciation of E2F-1 as a conditional tumor suppressor. E2F-1 can induce both apoptosis and S-phase transition and whether E2F-1 acts as an oncogene or a tumor-suppressor gene may depend on the extent to which E2F-1 induces apoptosis as opposed to G1/S transition.