The dual role of ultraspiracle, the Drosophila retinoid X receptor, in the ecdysone response
The dual role of ultraspiracle, the Drosophila retinoid X receptor, in the ecdysone response
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DOI：
10.1073/pnas.061437798
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发表时间：
2001-03-27
影响因子：
11.1
通讯作者：
McKeown, M
中科院分区：
文献类型：
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作者：
Ghbeish, N;Tsai, CC;McKeown, M
果蝇类视黄醇X受体的同源物超异二聚体（USP）与蜕皮激素受体（EcR）形成一个功能复合物，通过激活和抑制蜕皮激素反应基因的表达来介导类固醇蜕皮激素的作用。与其他类视黄醇X受体异源二聚体一样，EcR/USP以配体调节的方式影响基因转录。我们使用体内、细胞培养和生化方法分析了两个usp等位基因usp(3)和usp(4)的功能，它们编码具有缺陷dna结合域的稳定蛋白。我们观察到USP既能激活也能抑制外皮激素反应的broad复合物（BrC-Z1）的ZZ异构体。BrC-Z1和EcR （EcR本身是一种蜕皮激素反应基因）的激活可以由USP3和USP4突变蛋白介导。在培养的细胞中，USP3和USP4也激活一种蜕皮激素反应元件hsp27EcRE。这些结果与蛋白空等位基因usp(2)不同，后者不能介导激活[Schubiger， M, & Truman， J， W. (2000) Development 127, 1151-1159]。BrC-Z1的抑制在所有三个usp等位基因中都受到损害，这表明抑制涉及usp与DNA的关联。我们的研究结果区分了USP调节EcR特性的两种机制：一种机制涉及USP dna结合域，另一种机制仅通过配体结合域实现。这些新发现的性质可能暗示了类视黄酮X受体的类似性质。
The Drosophila homolog of the retinoid X receptor, ultraspiracle (USP), heterodimerizes with the ecdysone receptor (EcR) to form a functional complex that mediates the effects of the steroid molting hormone ecdysone by activating and repressing expression of ecdysone response genes. As with other retinoid X receptor heterodimers, EcR/USP affects gene transcription in a ligand-madulated manner. We used in vivo, cell culture, and biochemical approaches to analyze the functions of two usp alleles, usp(3) and usp(4), which encode stable proteins with defective DNA-binding domains. We observed that USP is able to activate as well as repress the ZZ isoform of the ecdysone-responsive broad complex (BrC-Z1). Activation of BrC-Z1 as well as EcR, itself an ecdysone response gene, can be mediated by both the USP3 and USP4 mutant proteins. USP3 and USP4 also activate an ecdysone-responsive element, hsp27EcRE, in cultured cells. These results differ from the protein null allele, usp(2), which is unable to mediate activation [Schubiger, M, & Truman, J, W. (2000) Development 127, 1151-1159]. BrC-Z1 repression is compromised in all three usp alleles, suggesting that repression involves the association of USP with DNA. Our results distinguish two mechanisms by which USP modulates the properties of EcR: one that involves the USP DNA-binding domain and one that can be achieved solely through the ligand-binding domain. These newly revealed properties of USP might implicate similar properties for retinoid X receptor.