MafB is an interaction partner and repressor of Ets-1 that inhibits erythroid differentiation.
Using a yeast one-hybrid screen with a DNA-bound Ets-1 protein, we have identified MafB, an AP-1 like protein, as a direct interaction partner. MafB is specifically expressed in myelomonocytic cells and binds to the DNA-binding domain of Ets-1 via its basic region or leucine-zipper domain. Furthermore, it represses Ets-1 transactivation of synthetic promoters containing Ets binding sites and inhibits Ets-1-mediated transactivation of the transferrin receptor, which is known to be essential for erythroid differentiation. Accordingly, overexpression of MafB in an erythroblast cell line down-regulates the endogenous transferrin receptor gene and inhibits differentiation without affecting cell proliferation. These results highlight the importance of inhibitory interactions between transcription factors in regulating lineage-specific gene expression.
Sieweke
M H
MH
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Tekotte
H
H
Frampton
J
J
Graf
T
T
D000818:Animals; D030161:Avian Proteins; D001483:Base Sequence; D001665:Binding Sites / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D002999:Clone Cells / Q000502:physiology; D018076:DNA, Complementary / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004900:Erythroblasts / Q000166:cytology* / Q000502:physiology; D051790:G-Box Binding Factors; D005786:Gene Expression Regulation / Q000502:physiology; D005820:Genetic Testing; D006410:Hematopoiesis / Q000235:genetics; D008264:Macrophages / Q000502:physiology; D051258:MafB Transcription Factor; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D011990:Receptors, Transferrin / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014714:Vertebrates; D015003:Yeasts / Q000235:genetics
D030161:Avian Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051790:G-Box Binding Factors; D051258:MafB Transcription Factor; D015513:Oncogene Proteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011990:Receptors, Transferrin; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C091157:maf-B protein, chicken; D011505:Protein-Tyrosine Kinases