The DEAD box protein DP103 is a regulator of steroidogenic factor-1

The nuclear receptor steroidogenic factor-1 (SF-1) is essential for develop ment of the gonads, adrenal gland, and the ventromedial hypothalamic nucleu s. It also regulates the expression of pivotal steroidogenic enzymes and ot her important proteins in the reproductive system. We sought to elucidate t he mechanisms that govern the transcriptional activity of SF-1, We demonstr ate here that a previously uncharacterized domain, located C-terminal to th e DNA binding domain of SF-1, exhibits transcriptional repression function, Point mutations in this domain markedly potentiate the transcriptional act ivity of native SF-1. Using an SF-1 region that spans this proximal repress ion domain as bait in a yeast two-hybrid system, we cloned an SF-1 interact ing protein that is homologous to human DP103, a member of the DEAD box fam ily of putative RNA helicases. DP103 directly interacts with the proximal r epression domain of SF-1, and mutations in this domain abrogate its interac tion with DP103, DP103 is expressed predominantly in the testis and is also expressed at a lower level in other steroidogenic and nonsteroidogenic tis sues. Functionally, DP103 exhibits a native transcriptional repression func tion that localizes to the C-terminal region of the protein and represses t he activity of wild-type, but not mutant, SF-1, Together, the physical and functional interaction of DP103 with a previously unrecognized repression d omain within SF-1 represents a novel mechanism for regulation of SF-1 activ ity.