title: The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila.
abstract: S6 kinases (S6Ks) act to integrate nutrient and insulin signaling pathways and, as such, function as positive effectors in cell growth and organismal development. However, they also have been shown to play a key role in limiting insulin signaling and in mediating the autophagic response. To identify novel regulators of S6K signaling, we have used a Drosophila-based, sensitized, gain-of-function genetic screen. Unexpectedly, one of the strongest enhancers to emerge from this screen was the nuclear receptor (NR), Drosophila hormone receptor 3 (DHR3), a critical constituent in the coordination of Drosophila metamorphosis. Here we demonstrate that DHR3, through dS6K, also acts to regulate cell-autonomous growth. Moreover, we show that the ligand-binding domain (LBD) of DHR3 is essential for mediating this response. Consistent with these findings, we have identified an endogenous DHR3 isoform that lacks the DBD. These results provide the first molecular link between the dS6K pathway, critical in controlling nutrient-dependent growth, and that of DHR3, a major mediator of ecdysone signaling, which, acting together, coordinate metamorphosis.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. montagne@cgm.cnrs-gif.fr
authors.forename: Jacques
authors.initials: J
authors.lastname: Montagne
authors.forename: Caroline
authors.initials: C
authors.lastname: Lecerf
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Parvy
authors.forename: Janis M
authors.initials: JM
authors.lastname: Bennion
authors.forename: Thomas
authors.initials: T
authors.lastname: Radimerski
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Ruhf
authors.forename: Frederic
authors.initials: F
authors.lastname: Zilbermann
authors.forename: Nicole
authors.initials: N
authors.lastname: Vouilloz
authors.forename: Hugo
authors.initials: H
authors.lastname: Stocker
authors.forename: Ernst
authors.initials: E
authors.lastname: Hafen
authors.forename: Sara C
authors.initials: SC
authors.lastname: Kozma
authors.forename: George
authors.initials: G
authors.lastname: Thomas
mesh_terms: D000818:Animals; D004330:Drosophila / Q000737:chemistry / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008675:Metamorphosis, Biological; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; C106186:Hr3 protein, Drosophila; D018160:Receptors, Cytoplasmic and Nuclear; D019893:Ribosomal Protein S6 Kinases
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