A movable and regulable inactivation function within the steroid binding domain of the glucocorticoid receptor.
The glucocorticoid receptor is a signal transducer that interacts both with the signal and with the genes it regulates. We showed previously that nuclear localization of the receptor requires hormone binding. We have now constructed recombinant receptors that relieve hormonal control of nuclear localization, and we demonstrate that the DNA binding/transcriptional regulatory functions of the receptor are also regulated directly by hormone. Surprisingly, regulation by the steroid binding domain appears to be relatively independent of protein structure. For example, regulation is maintained when the steroid binding region is repositioned from the C-terminus to the N-terminus of the receptor. Furthermore, the activity of an unrelated protein, the adenovirus E1A gene product, becomes hormone regulated upon fusion to the steroid binding domain. We speculate that the inhibitory effect of the unliganded steroid binding domain may be mediated by heat shock protein hsp90, which binds selectively to the unliganded receptor.
Picard
D
D
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Salser
S J
SJ
Yamamoto
K R
KR
D017456:Adenovirus Early Proteins; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D010957:Plasmids; D011487:Protein Conformation; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D017456:Adenovirus Early Proteins; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D006360:Heat-Shock Proteins; D009856:Oncogene Proteins, Viral; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D003907:Dexamethasone