Document Detail


Functional conservation of Drosophila FTZ-F1 and its mammalian homologs suggests ligand-independent regulation of NR5A family transcriptional activity.
MedLine Citation:
PMID:  23340581     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Drosophila Ftz-F1 is an orphan nuclear receptor required for segmentation and metamorphosis. Its mammalian orthologs, SF-1 and LRH-1, function in sexual development and homeostasis, and have been implicated in stem cell pluripotency maintenance and tumorigenesis. These NR5A family members bind DNA as monomers and strongly activate transcription. However, controversy exists as to whether their activity is regulated by ligand-binding. Structural evidence suggested that SF-1 and human LRH-1 bind regulatory ligands, but mouse LRH-1 and Drosophila FTZ-F1 are active in the absence of ligand. We found that Dm-Ftz-F1 and mLRH-1, thought not to bind ligand, or mSF-1 and hLRH-1, predicted to bind ligand, each efficiently rescued the defects of Drosophila ftz-f1 mutants. Further, each correctly activated expression of a Dm-Ftz-F1 target gene in Drosophila embryos. The functional equivalence of ftz-f1 orthologs in these sensitive in vivo assays argues against specific activating ligands for NR5A family members.
Authors:
Yong Lu; W Ray Anderson; Hua Zhang; Siqian Feng; Leslie Pick
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-23
Journal Detail:
Title:  Development genes and evolution     Volume:  -     ISSN:  1432-041X     ISO Abbreviation:  Dev. Genes Evol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9613264     Medline TA:  Dev Genes Evol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Cell Biology & Molecular Genetics, University of Maryland, 4112 Plant Sciences Building, College Park, MD, 20742, USA.
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