title: Functional conservation of Drosophila FTZ-F1 and its mammalian homologs suggests ligand-independent regulation of NR5A family transcriptional activity.
abstract: 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: Cell Biology & Molecular Genetics, University of Maryland, 4112 Plant Sciences Building, College Park, MD 20742, USA.
authors: Yong
authors: Y
authors: Lu
authors: W Ray
authors: WR
authors: Anderson
authors: Hua
authors: H
authors: Zhang
authors: Siqian
authors: S
authors: Feng
authors: Leslie
authors: L
authors: Pick
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D051379:Mice; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C499712:nuclear hormone receptor FTZ-F1, Drosophila