The transcriptional integrator CREB-binding protein mediates positive cross talk between nuclear hormone receptors and the hematopoietic bZip protein p45/NF-E2
The transcriptional integrator CREB-binding protein mediates positive cross talk between nuclear hormone receptors and the hematopoietic bZip protein p45/NF-E2
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DOI：
10.1128/mcb.17.3.1407
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发表时间：
1997-03-01
影响因子：
5.3
通讯作者：
Lazar, MA
中科院分区：
文献类型：
--
作者：
Cheng, XB;Reginato, MJ;Lazar, MA
甲状腺激素（T3）和维甲酸（RA）在红细胞生成中起重要作用。我们发现造血细胞特异性bZip蛋白p45/NF-E2与T3受体（TR）和RA受体（RAR）相互作用，但不与维甲酸X受体相互作用。核受体的DNA结合结构域和p45/NF-E2的亮氨酸拉链区之间存在相互作用，但同源配体显著增强。值得注意的是，TR和RAR的配体依赖性反式激活被p45/NF-E2显著增强。p45/NF-E2的这种作用被maf样蛋白p18阻止，其作为DNA上的p45/NF-E2的异源二聚体起积极作用。通过p45/NF-E2增强激素作用需要其激活结构域，其与多方面的辅激活因子环AMP反应元件蛋白结合蛋白（CBP）强烈相互作用。CBP与p45/NF-E2相互作用的区域是介导AP 1转录因子抑制BMP 1刺激的转录的相同相互作用结构域。CBP的bZip相互作用结构域的过表达特异性地消除了TR和p45/NF-E2之间的正向串扰。因此，p15/NF-E2和核激素受体之间的正串扰需要这些因子之间的直接蛋白质-蛋白质相互作用，并且与CBP，其整合来自两个反式激活结构域的正信号提供了增强造血细胞中激素作用的新机制。
Thyroid hormone (T3) and retinoic acid (RA) play important roles in erythropoiesis. We found that the hematopoietic cell-specific bZip protein p45/NF-E2 interacts with T3 receptor (TR) and RA receptor (RAR) but not retinoid X receptor. The interaction is between the DNA-binding domain of the nuclear receptor and the leucine zipper region of p45/NF-E2 but is markedly enhanced by cognate ligand. Remarkably, ligand-dependent transactivation by TR and RAR is markedly potentiated by p45/NF-E2. This effect of p45/NF-E2 is prevented by maf-like protein p18, which functions positively as a heterodimer with p45/NF-E2 on DNA. Potentiation of hormone action by p45/NF-E2 requires its activation domain, which interacts strongly with the multifaceted coactivator cyclic AMP response element protein-binding protein (CBP). The region of CBP which interacts with p45/NF-E2 is the same interaction domain that mediates inhibition of hormone-stimulated transcription by AP1 transcription factors. Overexpression of the bZip interaction domain of CBP specifically abolishes the positive cross talk between TR and p45/NF-E2. Thus, positive cross talk between p15/NF-E2 and nuclear hormone receptors requires direct protein-protein interactions between these factors and,vith CBP, whose integration of positive signals from two transactivation domains provides a novel mechanism for potentiation of hormone action in hematopoietic cells.