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

Miyuki Yussa, Ulrike Löhr, Kai Su, Leslie Pick

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)39-53
Number of pages15
JournalMechanisms of Development
Volume107
Issue number1-2
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Ftz
  • Homeodomain
  • Nuclear hormone receptor
  • SF-1
  • Transcription regulation

ASJC Scopus subject areas

  • Embryology
  • Developmental Biology

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