@article{b97d56d117a8449885e19a41bf321c15,
title = "The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathway",
abstract = "Ecdysteroid pulses trigger the major developmental transitions during the Drosophila life cycle. These hormonal responses are thought to be mediated by the ecdysteroid receptor (EcR) and its heterodimeric partner Ultraspiracle (USP). We provide evidence for a second ecdysteroid signaling pathway mediated by DHR38, the Drosophila ortholog of the mammalian NGFI-B subfamily of orphan nuclear receptors. DHR38 also heterodimerizes with USP, and this complex responds to a distinct class of ecdysteroids in a manner that is independent of EcR. This response is unusual in that it does not involve direct binding of ecdysteroids to either DHR38 or USP. X-ray crystallographic analysis of DHR38 reveals the absence of both a classic ligand binding pocket and coactivator binding site, features that seem to be common to all NGFI-B subfamily members. Taken together, these data reveal the existence of a separate structural class of nuclear receptors that is conserved from fly to humans.",
author = "Baker, {Keith D.} and Shewchuk, {Lisa M.} and Tatiana Kozlova and Makoto Makishima and Annie Hassell and Bruce Wisely and Caravella, {Justin A.} and Lambert, {Millard H.} and Reinking, {Jeffrey L.} and Henry Krause and Thummel, {Carl S.} and Willson, {Timothy M.} and Mangelsdorf, {David J.}",
note = "Funding Information: We thank Drs. Larry Gilbert and James Warren for ecdysteroid ligands and Shawn Williams for organizing the structural studies. We thank Tingwan Sun, Andy Shulman, and other members of the Mango lab for critically reading the manuscript. Structural data were collected at beamline 17-ID in the facilities of the Industrial Macromolecular Crystallography Association Collaborative Access Team (IMAT-CAT) at the Advanced Photon Source. These facilities are supported by the companies of the Industrial Macromolecular Crystallography Association through a contract with Illinois Institute of Technology (ITT), executed through the ITT's Center for Synchrotron Radiation Research and Instrumentation. D.J.M. and C.S.T. are investigators, and M.M. and T.K. are associates of the Howard Hughes Medical Institute (HHMI). This work was funded by HHMI (D.J.M. and C.S.T.) and the Robert A. Welch Foundation (D.J.M.). ",
year = "2003",
month = jun,
day = "13",
doi = "10.1016/S0092-8674(03)00420-3",
language = "English (US)",
volume = "113",
pages = "731--742",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",
}