Context dependent roles for RB-E2F transcriptional regulation in tumor suppression

The Rb/E2F pathway: expanding roles and emerging paradigms.

Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation.

Oncogene-induced cellular senescence is well documented, but little is known about how infinite cell proliferation induced by loss of tumor suppressor genes is antagonized by cellular functions. Rb heterozygous mice generate Rb-deficient C cell adenomas that progress to adenocarcinomas following biallelic loss of N-ras. Here, we demonstrate that pRb inactivation induces aberrant expression of f...

The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F.

Recent experiments have shown that the E2F transcription factor is in a complex with the RB1 gene product. The E2F-pRB complex can be reconstituted in an in vitro assay using a GST-RB fusion protein isolated from Escherichia coli. This interaction is dependent on pRB sequences involved in E1A/T-antigen binding as well as carboxy-terminal pRB sequences that are not necessary for E1A/T binding. M...

Noninvasive assessment of E2F-1-mediated transcriptional regulation in vivo.

Targeted therapies directed against individual cancer-specific molecular alterations offer the development of disease-specific and individualized treatment strategies. Activation of the transcription factor E2F-1 via alteration of the p16-cyclinD-Rb pathway is one of the key molecular events in the development of gliomas. E2F-1 binds to and activates the E2F-1 promoter in an autoregulatory mann...

Title Rb Regulates DNA Damage Response and Cellular Senescence through E2F-Dependent Suppression of N-Ras Isoprenylation