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

• Published in: Cell cycle (Georgetown, Tex.) Vol. 7; no. 12; pp. 1776 - 1781
• Main Authors: Palacios, Gustavo, Talos, Flaminia, Nemajerova, Alice, Moll, Ute M, Petrenko, Oleksi
• Format: Journal Article
• Language: English
• Published: United States 15-06-2008
• Subjects: Animals; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cells, Cultured; Cycle; DNA Damage; E2F1 Transcription Factor - genetics; E2F1 Transcription Factor - physiology; Landes; Mice; Mice, Knockout; Neoplasms, Experimental - epidemiology; Neoplasms, Experimental - genetics; Organogenesis; Phenotype; Proteins; Retinoblastoma Protein - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - physiology
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.7.12.6030

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.