The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila.
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.
Montagne
Jacques
J
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. montagne@cgm.cnrs-gif.fr
Lecerf
Caroline
C
Parvy
Jean-Philippe
JP
Bennion
Janis M
JM
Radimerski
Thomas
T
Ruhf
Marie-Laure
ML
Zilbermann
Frederic
F
Vouilloz
Nicole
N
Stocker
Hugo
H
Hafen
Ernst
E
Kozma
Sara C
SC
Thomas
George
G
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
D029721:Drosophila Proteins; C106186:Hr3 protein, Drosophila; D018160:Receptors, Cytoplasmic and Nuclear; D019893:Ribosomal Protein S6 Kinases
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