The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila.

Details

Serval ID
serval:BIB_3A593FA702F4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila.
Journal
PLoS Genetics
Author(s)
Montagne J., Lecerf C., Parvy J.P., Bennion J.M., Radimerski T., Ruhf M.L., Zilbermann F., Vouilloz N., Stocker H., Hafen E., Kozma S.C., Thomas G.
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
2010
Volume
6
Number
5
Pages
e1000937
Language
english
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.
Keywords
Animals, Drosophila/chemistry, Drosophila/genetics, Drosophila Proteins/chemistry, Drosophila Proteins/genetics, Female, Gene Expression Regulation, Developmental, Male, Metamorphosis, Biological, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear/chemistry, Receptors, Cytoplasmic and Nuclear/genetics, Ribosomal Protein S6 Kinases/genetics, Ribosomal Protein S6 Kinases/metabolism, Signal Transduction
Pubmed
Web of science
Open Access
Yes
Create date
06/01/2012 11:46
Last modification date
20/08/2019 13:30
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