Activation of the promoter of the orphan receptor SHP by orphan receptors that bind DNA as monomers

Small heterodimer partner (SHP) is an orphan nuclear receptor that lacks a conventional DNA binding domain. It interacts with several other members of the nuclear receptor superfamily and inhibits receptor transactivation, In order to characterize the regulation of SHP expression, a number of recept ors and other transcription factors were tested for effects on the SHP prom oter. Among these, the orphan receptor steroidogenic factor-1 (SF-1) was fo und to potently transactivate the SHP promoter. Detailed footprinting studi es show that the SHP promoter contains at least five SF-1 binding sites, an d mutagenesis studies demonstrate each of the three strongest binding sites is required for SF-1 transactivation, SHP is coexpressed with SF-1 in adre nal glands, but is also expressed in tissues that lack SF-1, including live r. However, liver expresses a close relative of SF-1, the orphan fetoprotei n transcription factor (FTF), and FTF can also transactivate the SHP promot er. These results suggest that alterations in the levels or activities of S F-1 or FTF could modulate SHP expression in appropriate tissues and thereby affect a variety of receptor dependent signaling pathways.