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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Cells, Cultured, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Fushi Tarazu Transcription Factors, Homeodomain Proteins, Insect Proteins, Molecular Sequence Data, Receptors, Cytoplasmic and Nuclear, Steroidogenic Factor 1, Transcription Factors
Proc. Natl. Acad. Sci. U.S.A.
Date: Oct. 23, 2001
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