E2F1 plays a direct role in Rb stabilization and p53-independent tumor suppression

To better understand the role of E2F1 in tumor formation, we analyzed spontaneous tumorigenesis in p53^-/-E2F1^+/+ and p53 ^-/-E2F1^-/- mice. We show that the combined loss of p53 and E2F1 leads to an increased incidence of sarcomas and carcinomas compared to the loss of p53 alone. E2F1-deficient tumors show wide chromosomal variation, indicative of genomic instability. Consistent with this, p53 ^-/-E2F1^-/- primary fibroblasts have a reduced capacity to maintain genomic stability when exposed to Sphase inhibitors or genotoxic drugs. A major mechanism of E2F1's contribution to genomic integrity lies in mediating stabilization and engagement of the Rb protein.