E2F1 plays a direct role in Rb stabilization and p53-independent tumor suppression.
June 29th, 2008 | by admin |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 S-phase inhibitors or genotoxic drugs. A major mechanism of E2F1\’s contribution to genomic integrity lies in mediating stabilization and engagement of the Rb protein.
Palacios G, Talos F, Nemajerova A, Moll UM, Petrenko O.
Department of Pathology, State University of New York at Stony Brook, Stony Brook, New York, USA.