Molecular cloning and characterization of a steroid receptor-binding regulator of G-protein signaling protein cDNA

Steroid hormone receptors are composed of six major functional domains, i.e . the A/B domains as the activation function I domain (AF-1), domain C as t he DNA-binding domain, domain D as a hinge domain and domain E/F as the lig and-dependent transcriptional domain (AF-2). They regulate gene transcripti on through interactions with various nuclear factors of their domains, such as AF-I and AF-2. We have insufficient knowledge of the function of the DN A-binding domain (domain C) except for its DNA-binding function or the hing e domain (domain D). Therefore, we attempted to identify factors interactin g with the domains by using a yeast two-hybrid system. Domains C and D of e strogen receptor alpha were used as a bait to isolate cDNA clones from a ra t ovary cDNA library. We isolated the cDNA clone of a novel steroid recepto r-binding protein bearing the regulator of G-protein signaling (RGS) design ated as SRB-RGS. The protein repressed the transcriptional activity of estr ogen receptor alpha, suggesting cross-talk of steroid hormones and peptide hormones (or growth factors) for signal transductions mediated by SRB-RGS. (C) 2001 Elsevier Science B.V. All rights reserved.