Disease relevance of E2F6

• Furthermore, inhibition of E2F, by overexpressing E2F6, was not sufficient to sensitise either proliferating keratinocytes or the squamous cell carcinoma cell line, KJD-1/SV40, to differentiation-inducing agents [1].
• Abnormal PcG protein expression in Hodgkin's lymphoma. Relation with E2F6 and NFkappaB transcription factors [2].
• E2F-6 contributes to gene silencing in a manner independent of retinoblastoma protein family members [3].

High impact information on E2F6

• Mapping studies indicate that RYBP binds within the known "repression domain" of E2F6 [4].
• The E2F6 transcription factor is a component of the mammalian Bmi1-containing polycomb complex [4].
• Taken together, these data suggest that E2F-6 can regulate a subset of E2F-dependent genes whose products are required for entry into the cell cycle but not for normal cell cycle progression [5].
• E2F-6 lacks pocket protein binding and transactivation domains, and it is a potent transcriptional repressor that contains a modular repression domain at its carboxyl terminus [5].
• Overproduction of E2F-6 had no specific effect on cell cycle progression in asynchronously growing Saos2 and NIH 3T3 cells, but it inhibited entry into S phase of NIH 3T3 cells stimulated to exit G0 [5].

Biological context of E2F6

• To determine which of the newly identified promoters were regulated by E2F6, we reduced the level of E2F6 by using RNA interference technology [6].
• E2F6 negatively regulates BRCA1 in human cancer cells without methylation of histone H3 on lysine 9 [6].
• E2F6, a member of the E2F family that lacks transactivation domains but contains specific suppressor domains, inhibits cytochrome c(1) promoter activity when co-transfected into HeLa cells, indicating that the E2F proteins modulate the cytochrome c(1) promoter in mammalian cells [7].
• However, E2F is not a general regulator of oxidative phosphorylation genes since three additional nuclear-encoded mitochondrial genes were unaffected by E2F1 or E2F6 [7].
• E2F6 is believed to repress E2F-responsive genes and therefore serve a role in cell cycle regulation [8].

Anatomical context of E2F6

• In this study, we examined the ability of E2F6 to act as the molecular switch required for E2F inhibition in order for keratinocytes to enter a terminal differentiation programme [1].
• Investigation of the relationship between E2F6 and RING1 by immunofluorescence and confocal analysis, in HL cell lines and paraffin sections, revealed co-expression of both proteins in the same tumour cells [2].
• To better elucidate the molecular mechanism of repression by E2F-6, we have purified the factor from cultured cells [3].

Associations of E2F6 with chemical compounds

• However, we found that the E2F6-regulated promoters did not contain histone H3 methylated at lysine 9 [6].

Physical interactions of E2F6

• E2F6 contains a DNA binding domain that is very similar to that of the other members of the E2F family of transcriptional regulators [6].

Other interactions of E2F6

• However, E2F6 cannot bind to all promoters that contain consensus E2F-binding sites [6].
• We report the isolation of RYBP, a recently identified member of the mammalian polycomb complex, as an E2F6-interacting protein [4].
• The cell cycle proteins associated with these tumors were E2F6, cyclins A, B1 and E, SKP2 and Topo IIalpha [9].

Analytical, diagnostic and therapeutic context of E2F6

• Therefore, we used a combination of chromatin immunoprecipitation and genomic microarrays to identify promoters bound by E2F6 in human cells [6].
• Sequence analysis reveals that AtE2F1 and AtE2F3 are closely related to previously identified plant E2Fs, whereas AtE2F2 is related to human E2F6 and Drosophila dE2F2 which are unusual in lacking transcriptional activation potential [10].
• TGFbeta1 also affected expression of E2F6, p57Kip2, G(q)alpha, hnRNP A1 and myosin light chain proteins as shown by immunoblotting [11].

References