Disease relevance of Mafk

• Taken together, these results provide direct evidence that NF-E2 gene is essential for globin transcription and suggest that perturbation in expression of this transcription factor may contribute to erythroleukemia progression [1].
• Thus, a quantitative embryonic platelet defect (severe thrombopenia secondary to NF-E2 deficiency) is associated with an embryonic growth retardation and reduced vascularisation of the placenta [2].

High impact information on Mafk

• To determine an in vivo role for p18 NF-E2 protein we disrupted the p18 NF-E2-encoding gene by homologous recombination in murine embryonic stem cells and generated p18 NF-E2-/- mice [3].
• Conditional expression of the ubiquitous transcription factor MafK induces erythroleukemia cell differentiation [4].
• In one erythroleukemia cell line the expression of NF-E2 p45 is undetectable due to proviral integration in one allele and loss of the other allele [1].
• Here we show that genomic sequences adjacent to Fli-2 correspond to the coding region of the erythroid-specific DNA binding protein NF-E2 p45 [1].
• These findings suggest that Scl acts up-stream of NF-E2 expression to control megakaryocyte development and platelet release in settings of thrombopoietic stress [5].

Biological context of Mafk

• The ubiquitous subunit of the globin enhancer-binding protein NF-E2 (Nfe2u) maps to mouse chromosome 5 [6].
• While the NF-E2 DNA sequence has been shown to be important for erythroid-specific gene regulation, a growing list of other genes may also be regulated through the same, or very similar, cis elements in non-erythroid cells [7].
• The presence of NF-E2 mRNA in HL-60 cells was demonstrated by reverse-transcription PCR amplification of the cDNA and Northern blot analysis [8].
• A 9-fold transactivation of luciferase (luc) reporter gene expression had been detected when NF-E2 cDNA was co-expressed with a TS promoter/luc construct [8].
• Internal sequence deletion and oligonucleotide competition established that a binding sequence for NF-E2 in PPRS1 (-60 tgctgattcat -50) was important for enhancing TS promoter activity in HL-60 cells [8].

Anatomical context of Mafk

• Here we present evidence that the large subunit of mammalian NF-E2, p45, is sumoylated in vivo in human erythroid K562 cells and in mouse fetal liver [9].
• These data together point to a model of mammalian beta-like globin gene activation by sumoylated p45/NF-E2 in erythroid cells [9].

Other interactions of Mafk

• Mutational studies further demonstrated that NF-E2/AP-1 and Sp1 exerted activating and repressive, respectively, effects on the promoter [10].

Analytical, diagnostic and therapeutic context of Mafk

• Preparative electrophoretic mobility shift assays coupled to Western analysis identified NF-E2-related proteins 1 and 2 and JunD in complexes assembled on AREs [11].

References