Disease relevance of E2F5

• Human E2F5 gene is oncogenic in primary rodent cells and is amplified in human breast tumors [1].
• Epidermal keratinocyte differentiation is accompanied by differential regulation of E2F genes, including up-regulation of E2F-5 and its concomitant association with the retinoblastoma family protein p130 [2].
• Involvement of protein kinase C and E2F-5 in euxanthone-induced neurite differentiation of neuroblastoma [3].

High impact information on E2F5

• However, in contrast to E2F-1, E2F-4 and E2F-5 fail to bind pRb in a two-hybrid assay [4].
• These findings suggest that E2F-4 and E2F-5 may contribute to the regulation of early G1 events including the G0/G1 transition [4].
• By using a specific E2F-5 antiserum, we found that under physiological conditions, E2F-5 interacts preferentially with p130 [5].
• Indeed, E2F-5 is exported from the nucleus through leptomycin B-sensitive, CRM1-mediated transport, through a region corresponding to amino acid residues 130-154 [2].
• Because E2F-5 is predominantly cytoplasmic in undifferentiated keratinocytes and in other intact cells, we also examined whether this protein is subjected to active nuclear export [2].

Biological context of E2F5

• E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle [4].
• This suggests that E2F5 behaves like a MYC-type cooperating oncogene in functional assays, prompting us to monitor potential amplifications of the E2F5 gene in primary human tumors [1].
• The E2F4 and E2F5 proteins specifically associate with the Rb-related p130 protein in quiescent cells to repress transcription of various genes encoding proteins important for cell growth [6].
• We have also demonstrated the presence of a strong transactivation domain at the carboxy terminus (273-346 amino acid residues) of E2F-5 protein [7].
• Alterations at the transcriptional level were identified, namely, upregulation of JUN and E2F5 [8].

Anatomical context of E2F5

• Moreover, they show a unique pattern of expression in synchronized human keratinocytes: E2F-4 and E2F-5 mRNA expression is maximal in mid-G1 phase before E2F-1 expression is detectable [4].
• 5-kb E2F5 transcript was also detected in some tumors and tumor cell lines [1].
• The distribution of E2F-5 mRNA among adult rat tissues and the temporal pattern of its expression during the cell cycle of vascular smooth muscle cells are distinctly different from that of E2F-1 [9].
• We have previously shown that LAP2beta, an integral nuclear-envelope protein that contains the chromatin-binding LEM domain, was able to repress the transcriptional activity of the E2F5-DP3 heterodimer [10].
• Novel genes expressed in adipocytes included E2F5 transcriptional factor and SMARC (SWI/SNF-related, matrix associated, actin-dependent regulator of chromatin) [11].

Associations of E2F5 with chemical compounds

• In conclusion, these results indicated that the transcription factor E2F-5 was actively involved in the regulation of euxanthone-induced neurite outgrowth via PKC pathway [3].

Regulatory relationships of E2F5

• We show that E2F5 can promote the formation of morphologically transformed foci in primary baby rat kidney cells (BRK) when it is overexpressed in the presence of its heterodimeric partner DP1 and activated RAS [1].
• It was found that p53 specifically inhibited activated transcription by E2F-5 but not by E2F-1 [12].

Other interactions of E2F5

• E2F-5, only in conjunction with DP1, promoted cell cycle progression [13].
• We found that, consistent with a role for E2F5 in transcriptional repression, E2F5's binding partner p130, like Rb, could also actively repress transcription when directly bound to a target promoter [14].
• The three genes showed ICN, albeit at variable incidence and levels of amplification, with the ICN of E2F5 occurring concomitantly with those of MOS and/or MYC in almost half of the cases [1].
• Go6976, a protein kinase C (PKC) alpha/betaI inhibitor, was found to inhibit neuritogenesis and expression of E2F-5 in the euxanthone-treated BU-1 cells, while SH-6, the Akt/PKB inhibitor, had no inhibitory effect [3].
• E2F-2 and E2F-5 were not detectable [15].

Analytical, diagnostic and therapeutic context of E2F5

• We have conducted a genome-wide screen using CpG island microarray analysis to identify novel promoters bound by E2F3 and E2F5 in human keratinocytes [16].

References