This holistic approach identified E2F1, a known mediator of the Rb tumor suppressor, as a transcriptional collaborator of EZH2 in castration-resistant prostate cancer.
We established a gene expression signature of Rb loss-of-function (RBsig) by identifying genes correlated with E2F1 and E2F2 expression in breast cancers within The Cancer Genome Atlas.
A knock-in mutation of the ATM phosphorylation site on E2F1 (S29A) prevents the interaction between E2F1 and TopBP1 and recruitment of RB, E2F1, and BRG1 to DSBs.
Here we illustrate the usefulness of the dual luciferase reporter assay to detect E2F-mediated transcriptional activity upon overexpression of E2F1 in cultured cells as readout for RB status and function.
Immunoprecipitation assay and ChIP-quantitative PCR results showed that FGF9-induced Rb phosphorylation led to the dissociation of Rb-E2F1 complexes and thereby enhanced the transactivations of E2F1 target genes, Cyclin D1, Cyclin E1 and Cyclin A1.
Additionally, identification of protumorigenic transcriptional networks specific to RB loss that were validated in clinical samples demonstrated the ability of RB loss to differentially reprogram E2F1 in human cancers.
These promoter regions are known to be bound by the E2F family proteins (E2F-1 to E2F-8) and retinoblastoma (RB) family proteins (RB1, p107, and p130), among which E2F-4 and p130 were strongly up-regulated in HSP27-knockdown cells.
E2F1 and retinoblastoma (RB) tumor-suppressor protein not only regulate the periodic expression of genes important for cell proliferation, but also localize to DNA double-strand breaks (DSBs) to promote repair.
Retinoblastoma is a pediatric solid tumor of the retina activated upon homozygous inactivation of the tumor suppressor <i>RB1</i> VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway.
In addition, miR-598 was found to promote cell apoptosis and inactivate the protein kinase B (AKT) pathway in RB. miR-598 suppressed RB cell viability and metastasis through inhibiting E2F1 and inactivating AKT pathway, which may provide a new perspective for RB treatment.