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
Gustavo
G
Department of Pathology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Talos
Flaminia
F
Nemajerova
Alice
A
Moll
Ute M
UM
Petrenko
Oleksi
O
D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins