Cryptocephal, the Drosophila melanogaster ATF4, Is a Specific Coactivator for Ecdysone Receptor Isoform B2
Cryptocephal, the Drosophila melanogaster ATF4, Is a Specific Coactivator for Ecdysone Receptor Isoform B2
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DOI：
10.1371/journal.pgen.1002883
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发表时间：
2012-08-01
期刊：
影响因子：
4.5
通讯作者：
Hewes, Randall S.
中科院分区：
文献类型：
--
作者：
Gauthier, Sebastien A.;VanHaaften, Eric;Hewes, Randall S.
蜕皮激素受体是两种核受体的异源二聚体，蜕皮激素受体（EcR）和超螺旋（USP）。在果蝇中，三个EcR异构体共享共同的DNA和配体结合域，但这些蛋白质在其最n端区域不同，因此在其中包含的激活域（af1）中也不同。这些结构域的转录共激活因子赋予EcR同种异构体独特的转录调控特性，目前尚不清楚。激活转录因子4 （ATF4）是一种碱性亮氨酸拉链转录因子，在哺乳动物的应激反应中起核心作用。在这里，我们发现隐头蛋白（CRC）， ATF4的果蝇同源物，是一种对异构体B2特异性的皮质激素受体共激活因子。CRC与EcR-B2相互作用，促进蜕皮激素依赖性的蜕皮触发激素（ETH）的表达，ETH是昆虫蜕皮行为的重要调节因子。我们认为，这种相互作用解释了EcR异构体在转录特性上的一些差异，类似的相互作用可能是其他具有不同af1共激活因子的核受体活性差异的基础。
The ecdysone receptor is a heterodimer of two nuclear receptors, the Ecdysone receptor (EcR) and Ultraspiracle (USP). In Drosophila melanogaster, three EcR isoforms share common DNA and ligand-binding domains, but these proteins differ in their most N-terminal regions and, consequently, in the activation domains (AF1s) contained therein. The transcriptional coactivators for these domains, which impart unique transcriptional regulatory properties to the EcR isoforms, are unknown. Activating transcription factor 4 (ATF4) is a basic-leucine zipper transcription factor that plays a central role in the stress response of mammals. Here we show that Cryptocephal (CRC), the Drosophila homolog of ATF4, is an ecdysone receptor coactivator that is specific for isoform B2. CRC interacts with EcR-B2 to promote ecdysone-dependent expression of ecdysis-triggering hormone (ETH), an essential regulator of insect molting behavior. We propose that this interaction explains some of the differences in transcriptional properties that are displayed by the EcR isoforms, and similar interactions may underlie the differential activities of other nuclear receptors with distinct AF1-coactivators.