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

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.

SUBMITTER: Palacios G

PROVIDER: S-EPMC4012429 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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

Palacios Gustavo G Talos Flaminia F Nemajerova Alice A Moll Ute M UM Petrenko Oleksi O

Cell cycle (Georgetown, Tex.) 20080630 12

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 expos ...[more]

PMID: 18583939

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