Disease relevance of ELF4

• ELF4 is fused to ERG in a case of acute myeloid leukemia with a t(X;21)(q25-26;q22) [1].
• Arildone, a novel antiviral agent which blocks virion uncoating, was assessed for its ability to prevent paralysis and death in mice infected intracerebrally with a lethal dose of human poliovirus type-2 (strain MEF) [2].
• Here we show that MEF is modified by conjugation with SUMO-1/-2 (small ubiquitin-related modifier) both in mammalian cells and in Escherichia coli overexpressing human SUMO-1/-2 [3].
• RESULTS: Seropositivity rates and geometric mean titers (GMTs) for the Mahoney (type 1), MEF (type 2), and Saukett (type 3) poliovirus strains and the wild poliovirus type 1 strain were 99.3% (GMT--233.8), 98.6% (GMT--268.5), 99.3% (GMT--89.4), and 99.3% (GMT--139.5), respectively [4].
• Interestingly, antibody to a synthetic peptide of PV-1 capsid protein VP2 exhibited IIA activity against PV-2 strain MEF [5].

High impact information on ELF4

• From the embryo of this mouse, we prepared fibroblast cell lines, MEF-hC3G [6].
• The Cre-expressing MEF-hC3G showed impaired cell adhesion, delayed cell spreading and accelerated cell migration [6].
• We have previously shown that cyclin A-dependent phosphorylation of MEF largely restricts its activity to the G(1) phase of the cell cycle; we now show that MEF is a short-lived protein whose expression level also peaks during late G(1) phase [7].
• Overexpression of MEF drives cells through the G(1)/S transition, thereby promoting cell proliferation [7].
• MEF is an ETS-related transcription factor with strong transcriptional activating activity that affects hematopoietic stem cell behavior and is required for normal NK cell and NK T-cell development [7].

Chemical compound and disease context of ELF4

• Fifty-four ears with evidence of pneumococcus (Pn) in the first acute otitis media (AOM) in 38 infants and with prolongation or recurrence of the MEF during the follow-up were observed for 7-22 months for the presence of Pn by culture or of pneumococcal antigen (Pn-ag) by counterimmunoelectrophoresis or latex agglutination methods in their MEFs [8].

Biological context of ELF4

• Here, we investigate the role of PML nuclear body in MEF transactivation [9].
• This interaction stimulated MEF transcriptional activity, resulting in the up-regulation of endogenous lysozyme expression [9].
• The IL-8 promoter contains three ETS binding sites, and we identified the specific site that binds MEF and is required for MEF responsiveness [10].
• MEF-deficient mice have defects in natural killer cell and natural killer T cell development, suggesting a role for MEF in regulating innate immunity [10].
• We report a novel chromosomal translocation in AML, t(X;21)(q25-26;q22), resulting in a fusion transcript between two ETS domain family members, ELF4 (at Xq25) and ERG (at 21q22) [1].

Anatomical context of ELF4

• Myeloid Elf-1-like factor, an ETS transcription factor, up-regulates lysozyme transcription in epithelial cells through interaction with promyelocytic leukemia protein [9].
• MEF also functions in myeloid cells, where it can transactivate target genes [10].
• MEF expression was up-regulated by 5-azacytidine in some cancer cell lines [11].
• By immunostaining with CD31, a marker on vascular endothelial cells, we found that tumor angiogenesis was significantly suppressed in the tumors formed from MEF-overexpressing cells [11].
• In addition, the conditioned media from A549 cell cultures stimulated the migration of human umbilical vein endothelial cells, whereas conditioned media from MEF-overexpressing cell cultures had less of an effect [11].

Associations of ELF4 with chemical compounds

• Here, we demonstrate that KLF6 protein is rapidly degraded when apoptosis is induced via the intrinsic pathway by cisplatin, adriamycin, or UVB irradiation in multiple cell lines (HCT116, SW40, HepG2, PC3-M, Skov3, NIH-3T3, 293T, GM09706, and MEF, IMR-90) [12].
• We identified by point mutation that lysine 657 of MEF is the site for sumoylation [3].
• Compared to saline, isoproterenol was followed by significantly increased FEV1 and MEF values (P less than 0.05) at both 10 and 30 minutes after medication, indicating reduction in bronchoconstriction [13].
• After atenolol there was a decrease of FEV1 and MEF 50 at 5 h [14].
• Metoprolol caused an increase in resistance at 2 and 5 h and a fall in FEV1, VC, and MEF 50 at 2 and 5 h [14].

Regulatory relationships of ELF4

• In addition, heat-shock treatment induced the accumulation of MEF in endogenous PML nuclear bodies and enhanced MEF transactivation of lysozyme gene [9].
• Furthermore, IL-8 mRNA expression in vitro was significantly down-regulated in MEF-overexpressing cells, compared with A549 cells [11].
• Thus, our data indicate that MEF may play an important role in regulating HBD2 expression in epithelial cells [15].
• MEF contains a central ETS domain and is expressed in a variety of myeloid leukemia cell lines and in normal adult hematopoietic tissue such as spleen, thymus and peripheral blood, as well as non-hematopoietic tissue such as ovary, placenta and colon [16].

Other interactions of ELF4

• Thus, the recruitment of MEF to PML nuclear bodies may partly regulate lysozyme transcription in epithelial cells [9].
• These data demonstrates that MEF is an important regulator of IL-8 expression [10].
• Here, we show that PML stimulated MEF transcriptional activity, resulting in the up-regulation of endogenous HBD 2 expression [17].
• The relative expression (RE) of MEF, but not ELF-1, was significantly lower (P<0.0001) in AML with t(8;21) and t(15;17) compared with AML with normal karyotype [18].
• MEF overexpression induced morphological changes, such as the conversion of normally loose cell-cell contacts to strong interactions similar to those seen in the presence of matrix metalloproteinase (MMP) inhibitor BB94 [11].

Analytical, diagnostic and therapeutic context of ELF4

• To identify MEF target genes in a "myeloid" environment, we created an inducible expression system and used oligonucleotide microarrays to examine the transcript profile of HEL cells after induction of MEF expression [10].
• By gelatin zymography, Western blotting analysis, and immunohistochemistry, we found that the expression levels of MMP-9 and MMP-2 were significantly reduced in MEF-overexpressing tumors [11].
• The interaction between the EBS and MEF protein was further confirmed by electrophoretic mobility shift assay [15].
• We also report the chromosomal assignment of ELFR and ELF-1 to Xq26 and 13q13, respectively, by means of fluorescence in-situ hybridization (FISH) [19].
• Functional dissection of the ETS transcription factor MEF [20].

References