MafB is an interaction partner and repressor of Ets-1 that inhibits erythroid differentiation

MafB is an interaction partner and repressor of Ets-1 that inhibits erythroid differentiation
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DOI:
10.1016/s0092-8674(00)81081-8
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发表时间:
1996-04-05
期刊:
影响因子:
64.5
通讯作者:
Graf, T
Graf, T
中科院分区:
生物学1区
文献类型:
--
作者:
Sieweke, MH;Tekotte, H;Graf, T

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利用酵母与dna结合的Ets-1蛋白的单杂交筛选,我们已经确定了mapb,一种AP-1样蛋白,作为直接相互作用的伙伴。MafB在骨髓单核细胞中特异表达,并通过Ets-1的碱基区或亮氨酸拉链区与Ets-1的dna结合域结合。此外,它抑制含有Ets结合位点的合成启动子的Ets-1反激活,并抑制Ets-1介导的转铁蛋白受体的反激活,这是红细胞分化所必需的,因此,在红细胞系中,MafB过表达下调内源性转铁蛋白受体基因并抑制分化而不影响细胞增殖。这些结果强调了转录因子之间的抑制相互作用在调节谱系特异性基因表达中的重要性。
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.