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Science 12 August 1988:
Vol. 241. no. 4867, pp. 812 - 816
DOI: 10.1126/science.3043662
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Articles

Science, Vol 241, Issue 4867, 812-816
Copyright © 1988 by American Association for the Advancement of Science

articles

Signal transduction and transcriptional regulation by glucocorticoid receptor-LexA fusion proteins

PJ Godowski, D Picard, and KR Yamamoto

Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.

The glucocorticoid receptor regulates transcriptional initiation upon binding to its cognate hormone. A series of fusion genes was constructed to examine the mechanism of hormone-regulated transcriptional enhancement. The DNA binding domain of the bacterial LexA repressor was fused to receptor derivatives lacking the region that is necessary and sufficient for specific DNA binding and transcriptional enhancement at glucocorticoid response elements (GRE's). The resultant hybrid proteins activated transcription from promoters linked to the lex operator. Enhancement still required hormone binding by the hybrid receptor regardless of the exact positioning of the LexA binding domain within the protein. Thus, the unliganded hormone binding domain of the receptor acts as a strong but reversible inhibitor of receptor activity in a manner that is independent of the means by which the receptor recognizes DNA. The results also show directly that the receptor contains at least one "enhancement domain" other than that overlapping the GRE binding region; the second domain, enh2, occupies a region near the receptor amino terminus.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)