Department of Biochemistry and Molecular Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Mol Cell. 2011 Oct 7;44(1):51-61. doi: 10.1016/j.molcel.2011.07.033.
The Drosophila ecdysone receptor (EcR/Usp) is thought to activate or repress gene transcription depending on the presence or absence, respectively, of the hormone ecdysone. Unexpectedly, we found an alternative mechanism at work in salivary glands during the ecdysone-dependent transition from larvae to pupae. In the absense of ecdysone, both ecdysone receptor subunits localize to the cytoplasm, and the heme-binding nuclear receptor E75A replaces EcR/Usp at common target sequences in several genes. During the larval-pupal transition, a switch from gene activation by EcR/Usp to gene repression by E75A is triggered by a decrease in ecdysone concentration and by direct repression of the EcR gene by E75A. Additional control is provided by developmentally timed modulation of E75A activity by NO, which inhibits recruitment of the corepressor SMRTER. These results suggest a mechanism for sequential modulation of gene expression during development by competing nuclear receptors and their effector molecules, ecdysone and NO.
果蝇蜕皮激素受体 (EcR/Usp) 被认为可以根据激素蜕皮激素的存在或不存在来激活或抑制基因转录。出乎意料的是，我们在蜕皮激素依赖性的幼虫到蛹的过渡过程中在唾液腺中发现了一种替代机制在起作用。在没有蜕皮激素的情况下，蜕皮激素受体亚基都定位于细胞质中，血红素结合核受体 E75A 取代 EcR/Usp 在几个基因的常见靶序列上。在幼虫到蛹的过渡期间，由 EcR/Usp 激活基因到 E75A 抑制基因的转变是由蜕皮激素浓度的降低和 E75A 对 EcR 基因的直接抑制触发的。由 NO 对 E75A 活性的发育定时调节提供了额外的控制，NO 抑制了核心抑制剂 SMRTER 的募集。这些结果表明，在发育过程中，通过竞争核受体及其效应分子蜕皮激素和 NO 来连续调节基因表达的机制。
