Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor.
Using a combination of a transient expression assay and in vitro mutagenesis, we showed previously that the human glucocorticoid receptor (hGR) is composed of a series of discrete functional domains. Here we report the effects of selective deletion of each of these domains on hGR ability to activate transcription of the MTV-CAT fusion gene. Deletion of the immunogenic domain or the entire amino-terminal half of the protein reduces but does not abolish the ability of the hGR to induce transcriptional activation. Somewhat surprisingly, deletion of the steroid-binding domain engenders a constitutively active receptor, revealing that this domain normally represses receptor function. However, the central, cysteine-rich region contains all the information required for both DNA binding and trans-activation. Taken together, these data delineate a core domain in the hGR spanning 88 amino acids that determines both DNA-binding and transcriptional activation functions. This physical linkage distinguishes the glucocorticoid receptor from other described eukaryotic regulatory proteins, where these two functions have been shown to be separable.
D000818:Animals; D002460:Cell Line; D002872:Chromosome Deletion; D004247:DNA / Q000378:metabolism*; D005796:Genes; D006801:Humans; D009154:Mutation; D010957:Plasmids; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D011965:Receptors, Glucocorticoid; D004247:DNA