Segmentation gene product Fushi tarazu is an LXXLL motif-dependent coactivator for orphan receptor FTZ-F1.
Orphan receptors for whom cognate ligands have not yet been identified form a large subclass within the nuclear receptor superfamily. To address one aspect of how they might regulate transcription, we analyzed the mode of interaction between the Drosophila orphan receptor FTZ-F1 (NR5A3) and a segmentation gene product Fushi tarazu (FTZ). Strong interaction between these two factors was detected by use of the mammalian one- and two-hybrid interaction assays without addition of ligand. This interaction required the AF-2 core and putative ligand-binding domain of FTZ-F1 and the LXXLL motif of FTZ. The requirement of these elements was further confirmed by examination of their target gene expression in Drosophila embryos and observation of a cuticle phenotype in transgenic fly lines that express mutated factors. In Drosophila cultured cells, FTZ is required for FTZ-F1 activation of a FTZ-F1 reporter gene. These results reveal a resemblance in the mode of interaction between FTZ-F1 and FTZ and that of nuclear receptor-coactivator and indicate that direct interaction is required for regulation of gene expression by FTZ-F1. Thus, we propose that FTZ may represent a category of LXXLL motif-dependent coactivators for nuclear receptors.
Suzuki
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Institute for Virus Research, and Graduate School for Biostudies, Kyoto University, Kyoto 606-8507, Japan.
Kawasaki
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H
Yu
R T
RT
Ueda
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Umesono
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D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects*; D004330:Drosophila; D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019476:Insect Proteins; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000187:drug effects*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D019476:Insect Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C497169:ftz protein, Drosophila; C499712:nuclear hormone receptor FTZ-F1, Drosophila