Cryptocephal, the Drosophila melanogaster ATF4, Is a Specific Coactivator for Ecdysone Receptor Isoform B2

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Date
2012
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PLoS Genetics
Abstract
The ecdysone receptor is a heterodimer of two nuclear receptors, the Ecdysone receptor (EcR) and Ultraspiracle (USP). In $\textit{Drosophila melanogaster}$, 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 $\textit{Drosophila}$ 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.
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activating transcription factor 4, cryptocephal protein, ecdysis triggering hormone, ecdysone, ecdysone receptor, ecdysone receptor isoform B2, hormone, leucine zipper protein, messenger RNA, transcription factor, unclassified drug, amino terminal sequence, binding affinity, dimerization, down regulation, Drosophila melanogaster, ecdysis triggering hormone gene, gene, gene dosage, Gene Expression Regulation, gene switching, in vitro study, in vivo study, molting, mutational analysis, nonhuman, phenotype, Protein Binding, protein domain, protein expression, protein function, protein localization, protein protein interaction, transcription initiation, upregulation, Animals, DNA-Binding Proteins, Drosophila Proteins, Insect Hormones, Protein Isoforms, Protein Multimerization, Protein Structure, Tertiary, Receptors, Steroid, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Hexapoda, Mammalia, Activating Transcription Factor 4, 145891-90-3, Receptors, Steroid, cryptocephal protein, Drosophila, ecdysis-triggering hormone, Drosophila, ultraspiracle protein, Drosophila
Citation
Gauthier, S. A., VanHaaften, E., Cherbas, L., Cherbas, P., & Hewes, R. S. (2012). Cryptocephal, the drosophila melanogaster ATF4, is a specific coactivator for ecdysone receptor isoform B2. PLoS Genetics, 8(8). http://dx.doi.org/10.1371/journal.pgen.1002883
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© 2012 Gauthier et al
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