M. Yussa et al., The nuclear receptor Ftz-F1 and homeodomain protein Ftz interact through evolutionarily conserved protein domains, MECH DEVEL, 107(1-2), 2001, pp. 39-53
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 viv
o 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 de
fects of ftz-f1 mutants. This finding identified evolutionarily conserved d
omains of Ftz-F1 as critical for activity of this receptor in vivo. These d
omains function. at least in part. by mediating direct protein interactions
with Ftz. The Ftz-F1 DNA binding domain interacts strongly with Ftz and dr
amatically facilitates the binding of Ftz to target DNA. This interaction i
s augmented by a second interaction between the AF-2 domain of Ftz-F1 and t
he N-terminus of Ftz via an LRALL sequence in Ftz that is reminiscent of LX
XLL 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 h
and, influences Ftz-F1 activity by interacting with its AF-2 domain in a ma
nner that mimics a nuclear receptor coactivator. (C) 2001 Elsevier Science
Ireland Ltd. All rights reserved.