The nuclear receptor Ftz-F1 and homeodomain protein Ftz interact through evolutionarily conserved protein domains.

The Drosophila homeodomain protein Fushi Tarazu (Ftz) and its partner, the orphan receptor Ftz-F1, are members of two distinct families of DNA binding transcriptional regulators. Ftz and Ftz-F1 form a novel partnership in vivo as a Hox/orphan receptor heterodimer. Here we show that the murine Ftz-F1 ortholog SF-1 functionally substitutes ...
for Ftz-F1 in vivo, rescuing the defects of ftz-f1 mutants. This finding identified evolutionarily conserved domains of Ftz-F1 as critical for activity of this receptor in vivo. These domains function, at least in part, by mediating direct protein interactions with Ftz. The Ftz-F1 DNA binding domain interacts strongly with Ftz and dramatically facilitates the binding of Ftz to target DNA. This interaction is augmented by a second interaction between the AF-2 domain of Ftz-F1 and the N-terminus of Ftz via an LRALL sequence in Ftz that is reminiscent of LXXLL motifs in nuclear receptor coactivators. We propose that Ftz-F1 serves as a cofactor for Ftz by facilitating the selection of target sites in the genome that contain Ftz/Ftz-F1 composite binding sites. Ftz, on the other hand, influences Ftz-F1 activity by interacting with its AF-2 domain in a manner that mimics a nuclear receptor coactivator.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Conserved Sequence, DNA, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Embryo, Nonmammalian, Evolution, Molecular, Fushi Tarazu Transcription Factors, Gene Expression Regulation, Developmental, Homeodomain Proteins, Insect Proteins, Mice, Molecular Sequence Data, Mutation, Phenotype, Protein Binding, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear, Steroidogenic Factor 1, Transcription Factors, Transcription, Genetic, Zinc Fingers
Mech. Dev.
Date: Sep. 01, 2001
Download Curated Data For This Publication
203968
Switch View:
  • Interactions 2