Document Detail


dDOR is an EcR coactivator that forms a feed-forward loop connecting insulin and ecdysone signaling.
MedLine Citation:
PMID:  20888228     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND: Mammalian DOR was discovered as a gene whose expression is misregulated in muscle of Zucker diabetic rats. Because no DOR loss-of-function mammalian models are available, we analyze here the in vivo function of DOR by studying flies mutant for Drosophila DOR (dDOR).
RESULTS: We show that dDOR is a novel coactivator of ecdysone receptor (EcR) that is needed during metamorphosis. dDOR binds EcR and is required for maximal EcR transcriptional activity. In the absence of dDOR, flies display a number of ecdysone loss-of-function phenotypes such as impaired spiracle eversion, impaired salivary gland degradation, and pupal lethality. Furthermore, dDOR knockout flies are lean. We find that dDOR expression is inhibited by insulin signaling via FOXO.
CONCLUSION: This work uncovers dDOR as a novel EcR coactivator. It also establishes a mutual antagonistic relationship between ecdysone and insulin signaling in the fly fat body. Furthermore, because ecdysone signaling inhibits insulin signaling in the fat body, this also uncovers a feed-forward mechanism whereby ecdysone potentiates its own signaling via dDOR.
Authors:
Víctor A Francis; Antonio Zorzano; Aurelio A Teleman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-30
Journal Detail:
Title:  Current biology : CB     Volume:  20     ISSN:  1879-0445     ISO Abbreviation:  Curr. Biol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107782     Medline TA:  Curr Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1799-808     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, Heidelberg, Germany.
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Comment In:
Curr Biol. 2010 Oct 26;20(20):R884-6   [PMID:  20971430 ]

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