A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning.
In search of proteins which interact with activated steroid hormone receptors, 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 predominantly of hydrophilic amino acids and contains a putative bipartite nuclear localization signal. The in vitro translated receptor-associating protein runs in SDS/polyacrylamide gels with an apparent molecular 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 receptors--most notably, the estrogen and thyroid receptors. Binding also occurs with the glucocorticoid receptor complexed with the antiglucocorticoid RU 38486, with the estrogen receptor complexed with the antiestrogen 4-hydroxytamoxifen or ICI 164,384, and even with receptors not complexed with ligand. Association with steroid hormone receptors depends 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 variety of mammalian tissues.
Institut für Biologische Chemie, Universität Heidelberg, Germany.
M
M
Zeiner
U
U
Gehring
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D026563:LDL-Receptor Related Protein-Associated Protein; D008969:Molecular Sequence Data; D005810:Multigene Family; D011485:Protein Binding; D011944:Receptors, Androgen / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D011987:Receptors, Steroid / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D002352:Carrier Proteins; D018076:DNA, Complementary; D006023:Glycoproteins; D026563:LDL-Receptor Related Protein-Associated Protein; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D011994:Recombinant Proteins