Activation of the Promoter of the Orphan Receptor SHP by Orphan Receptors That Bind DNA as Monomers

作者：Yoon‐Kwang Lee, Keith L. Parker, Hueng‐Sik Choi, David D. Moore · 发表于：Journal of Biological Chemistry · 年份：1999 · DOI：10.1074/jbc.274.30.20869 · 被引用次数：105 · 研究领域：Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities、Estrogen and related hormone effects、Nuclear Receptors and Signaling

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.