Igarashi K, Kataoka K, Itoh K, Hayashi N, Nishizawa M, Yamamoto M
Department of Biochemistry, Tohoku University School of Medicine, Sendai, Japan.
Nature. 1994 Feb 10;367(6463):568-72. doi: 10.1038/367568a0.
Transcription factor NF-E2 is crucial for regulating erythroid-specific gene expression. Cloning of the NF-E2 p45 protein has revealed that it contains a basic region-leucine zipper (b-zip) domain which associates with another unidentified protein (of relative molecular mass 18,000) to form functional NF-E2. We show here that products of the maf proto-oncogene family, MafF, MafG and MafK (the small Maf proteins) which possess a b-zip DNA-binding domain but lack a canonical transactivation domain, directly control the DNA-binding properties of p45 by heterodimeric association with p45. Whereas homodimers of the small Maf proteins act as negative regulators, heterodimers composed of Maf and p45 support active transcription in vivo. These results indicate that one (or all) of the small Maf proteins is the second constituent chain required for NF-E2 activity, and that negative as well as positive regulation can be achieved through an NF-E2 site, depending on the equilibrium concentrations of p45 and the Maf proteins inside erythroid cells.
转录因子NF-E2对于调控红系特异性基因表达至关重要。NF-E2 p45蛋白的克隆显示，它含有一个碱性区域-亮氨酸拉链（b-zip）结构域，该结构域与另一种未鉴定的蛋白质（相对分子质量为18,000）结合形成功能性NF-E2。我们在此表明，maf原癌基因家族的产物MafF、MafG和MafK（小Maf蛋白）具有b-zip DNA结合结构域但缺乏典型的反式激活结构域，它们通过与p45异源二聚体结合直接控制p45的DNA结合特性。小Maf蛋白的同二聚体作为负调控因子，而由Maf和p45组成的异二聚体在体内支持活性转录。这些结果表明，小Maf蛋白中的一种（或全部）是NF-E2活性所需的第二条组成链，并且根据红系细胞内p45和Maf蛋白的平衡浓度，通过NF-E2位点可以实现负调控和正调控。
