E2F1 plays a direct role in Rb stabilization and p53-independent tumor suppression
2008 | journal article. A publication with affiliation to the University of Göttingen.
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- Authors
- Palacios, Gustavo; Talos, Flaminia; Nemajerova, Alice; Moll, Ute M.; Petrenko, Oleksi
- Abstract
- 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.
- Issue Date
- 2008
- Status
- published
- Publisher
- Landes Bioscience
- Journal
- Cell Cycle
- ISSN
- 1538-4101
- Sponsor
- NCI NIH HHS [R01 CA060664-13, R01 CA060664]