Disease relevance of EDF1

• The cDNA encoding EDF-1 was isolated by RNA fingerprinting from human endothelial cells exposed to human immunodeficiency virus type 1 Tat, a viral protein known to be angiogenic [1].
• In undifferentiated human teratocarcinoma (T2) cells we have previously shown that major immediate early gene expression is repressed by a differentiation specific nuclear factor MBF1, which binds to the imperfect dyad symmetry located upstream of the enhancer [2].

High impact information on EDF1

• A conserved glutamic acid/glutamine in the linker region underlies MBF1 specificity for a subgroup of bZIP factors [3].
• Analysis of Jun derivatives that selectively interact with these coactivators reveals that MBF1 is crucial for the response to oxidative stress, whereas Chameau is important for the response to chemical and osmotic stress [3].
• Both MBF1 and MBF2 are necessary to form a complex between BmFTZ-F1 and TBP [4].
• Neither MBF1, MBF2, nor a combination of them binds to DNA [4].
• In addition, 12-O-tetradecanoylphorbol-13-acetate treatment of human umbilical vein endothelial cell stimulates the nuclear translocation of EDF-1 [5].

Biological context of EDF1

• Here we report that (i) EDF-1 binds CaM in vitro and in vivo; (ii) EDF-1 is phosphorylated in vitro and in vivo by protein kinase C; and (iii) EDF-1-CaM interaction is modulated by the concentrations of Ca(2+) and by the phosphorylation of EDF-1 by protein kinase C both in vitro and in vivo [5].
• Human MBF1 (hMBF1) can bind to TBP and to the nuclear receptor Ad4BP, and is suggested to mediate Ad4BP-dependent transcriptional activation [6].
• In addition, the inhibition of EDF-1 translation by an antisense anti-EDF-1 construct results in the inhibition of endothelial cell growth and in the transition from a nonpolar cobblestone phenotype to a polar fibroblast-like phenotype [1].
• The deduced amino acid sequence of EDF-1 encodes a basic intracellular protein of 148 amino acids that is homologous to MBF1 (multiprotein-bridging factor 1) of the silkworm Bombyx mori and to H7, which is implicated in the early developmental events of Dictyostelium discoideum [1].
• MBF1 bridges the DNA-binding regions of these activators and the TATA-box binding protein (TBP), suggesting that MBF1 functions by recruiting TBP to promoters where the activators are bound [7].

Anatomical context of EDF1

• Recently, we described endothelial differentiation-related factor (EDF)-1 as a protein involved in the repression of endothelial cell differentiation (Dragoni, I., Mariotti, M., Consalez, G. G., Soria, M., and Maier, J. A. M. (1998) J. Biol. Chem. 273, 31119-31124) [5].
• The dual role of endothelial differentiation-related factor-1 in the cytosol and nucleus: modulation by protein kinase A [8].
• When recombinant MBF2 was added to the HeLa cell nuclear extract in the presence of MBF1 and FTZ622 bearing the DNA-binding region of FTZ-F1, it selectively activated transcription of the fushi tarazu gene [9].
• As persistent MBF-1 binding and enhancer activity are detected in gastrula embryos, we have studied the molecular mechanisms that prevent the bound MBF-1 from trans-activating the H2A promoter at this stage of development [10].
• MBF-1 is expressed in the unfertilized egg and in early and late developmental stages thus confirming that it is not a stage specific enhancer binding factor and that silencing of the alpha-H2A gene after hatching is not due to the lack of the transactivator [11].

Associations of EDF1 with chemical compounds

• We hypothesize that EDF-1 serves two main functions in endothelial cells as follows: (i) to bind CaM in the cytosol at physiologic concentrations of Ca(2+) and (ii) to act in the nucleus as a transcriptional coactivator through its binding to TBP [5].

Other interactions of EDF1

• BACKGROUND: Transcriptional activation of the Drosopohila melanogaster fushi tarzu gene by FTZ-F1 or its silkworm counterpart BmFTZ-F1 requires two cofactors MBF1 and MBF2 which do not directly bind to DNA [9].

Analytical, diagnostic and therapeutic context of EDF1

• N-terminal sequence analysis and NMR measurements revealed that this fragment originates from the C-terminal 80 residues of MBF1 and form a well structured C-terminal domain of MBF1, MBF1CTD [7].
• Here we used chromatin immunoprecipitation to demonstrate that MBF-1 occupies its site regardless of the transcriptional state of the H2A gene [10].
• STUDY DESIGN AND METHODS: This study examined the effect of filtration with three different filters (MBF1, MBF2, and MBF3) on MB concentration, residual cells, coagulation factors, and activation measures of coagulation, fibrinolysis, and complement in MB-treated (1 microM/L) plasma units [12].

References