A PROTEIN THAT INTERACTS WITH MEMBERS OF THE NUCLEAR HORMONE-RECEPTORFAMILY - IDENTIFICATION AND CDNA CLONING

In search of proteins which interact with activated steroid hormone re ceptors, we screened a human liver lambda gt11 expression library with the glucocorticoid receptor. We identified and cloned a cDNA sequence of 1322 bp that encodes a protein of 274 aa. This protein consists pr edominantly of hydrophilic amino acids and contains a putative biparti te nnclear localization signal. The in vitro translated receptor-assoc iating protein runs in SDS/polyacrylamide gels with an apparent molecu lar mass of 46 kDa. By use of the bacterially expressed fusion protein with glutathione S-transferase we have found that interaction is not limited to the glucocorticoid receptor but included other nuclear rece ptors-most notably, the estrogen and thyroid receptors, Binding also o ccurs with the glucocorticoid receptor complexed with the antiglucocor ticoid RU 38486, with the estrogen receptor complexed with the antiest rogen 4-hydroxytamoxifen or ICI 164,384, and even with receptors not c omplexed with ligand. Association with steroid hormone receptors depen ds on prior receptor activation-i.e., release from heat shock proteins . The sequence identified here appears to be a general partner protein for nuclear hormone receptors, with the gene being expressed in a var iety of mammalian tissues.