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 receptors and other transcription factors were tested for effects on the SHP promoter. Among these, the orphan receptor steroidogenic factor-1 (SF-1) was found to potently transactivate the SHP promoter. Detailed footprinting studies show that the SHP promoter contains at least five SF-1 binding sites, and mutagenesis studies demonstrate each of the three strongest binding sites is required for SF-1 transactivation. SHP is coexpressed with SF-1 in adrenal glands, but is also expressed in tissues that lack SF-1, including liver. However, liver expresses a close relative of SF-1, the orphan fetoprotein transcription factor (FTF), and FTF can also transactivate the SHP promoter. These results suggest that alterations in the levels or activities of SF-1 or FTF could modulate SHP expression in appropriate tissues and thereby affect a variety of receptor dependent signaling pathways.
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Y K
YK
Lee
K L
KL
Parker
H S
HS
Choi
D D
DD
Moore
D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*
D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D004247:DNA