MafB represses erythroid genes and differentiation through direct interaction with c-Ets-1.
Using a yeast interaction screen with a DNA-bound Ets-1 protein we have identified MafB as a direct interaction partner. This distant AP-1 relative, which is specifically expressed in myelomonocytic cells, binds to the DNA binding domain of Ets-1 via its basic region/leucine zipper domain. MafB represses Ets-1 transactivation of synthetic promoters containing Ets binding sites in yeast as well as avian cells. Both Ets-1 and Maf family proteins have been implicated in erythroid specific gene expression. Here we show that MafB inhibits Ets-1-mediated transactivation of the transferrin receptor, which is essential for heme synthesis and erythroid differentiation. Consequently, overexpression of MafB in an erythroblast cell line down-regulates the endogenous transferrin receptor gene and inhibits the cells' potential to differentiate into erythrocytes, without affecting cellular proliferation.
Sieweke
M H
MH
Tekotte
H
H
Frampton
J
J
Graf
T
T
D000818:Animals; D030161:Avian Proteins; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D004900:Erythroblasts / Q000166:cytology* / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology* / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006418:Heme / Q000096:biosynthesis; D016350:Leucine Zippers; D015513:Oncogene Proteins / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D011990:Receptors, Transferrin / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D030161:Avian Proteins; D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D006418:Heme