E2F1

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E2F1

A gene on chromosome 20q11.2 that encodes a member of the E2F family of DNA-binding transcription factors, which play a key role in regulating the cell cycle and tumour suppressor proteins. E2Fs are targets of transforming proteins of small DNA tumour viruses.
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An additional clinical-stage program includes compounds that activate the cell's DNA damage response mechanism mediated by the E2F-1 transcription factor.
The company's lead ACT program, based on the E2F-1 pathway, is partnered with Roche.
E2F-1 is believed to be the ultimate mediator of G1 to S progression by promoting the transcription of a wide range of genes essential for S phase, including cdc25A, cyclin E, and B-myb.
that relate to the ongoing development of: ARQ 621, a novel inhibitor of the Eg5 kinesin motor protein in Phase 1 clinical testing; ARQ 736, a novel inhibitor of BRAF in pre-clinical development; and ARQ 501, an activator of the DNA damage response mechanism mediated by the E2F-1 transcription factor that has completed initial clinical testing.
Following further investigation into the temporal sequence of the biochemical signal transduction cascade that leads to Hoechst 33342-induced apoptosis, Zhang and Kiechle report that the concentration of transcription factor E2F-1 increases intracellularly during this process.
Stress signals induce transcriptionally inactive E2F-1 independently of p53 and Rb.
Levels of E2F-1 expression are higher in lung metastasis of colon cancer as compared with hepatic metastasis and correlate with levels of thymidylate synthase.
1,2] Transcription factors of the E2F family, composed of E2F-1 through E2F-5, have been shown to play a key role in the regulation of cell proliferation[3-5] and apoptotic cell death.
In the present study, our findings show that Hoechst 33342 treatment of BC3H-1 myocytes and HL-60 cells significantly increased accumulation of E2F-1 protein and protein/E2F-1/oligonucleotide complexes in the nucleus of both cell lines after 3 hours.
E2F-1 Protein in Hoechst 33342- or Hoechst 33258--Treated Cells
The concentration of E2F-1 protein in nuclear extracts from BC3H-1 myocytes or HL-60 cells after Hoechst 33342 or Hoechst 33258 treatment was estimated by the gel mobility shift assay[13,30] If a protein in the nuclear extracts had a binding affinity for the E2F-1 binding site on the 30-bp, [[sup.
Additional clinical-stage programs include compounds that inhibit the Eg5 kinesin spindle protein and compounds that activate the cell's DNA damage response mechanism mediated by the E2F-1 transcription factor.