Agonist-Activated Glucocorticoid Receptor Inhibits Binding of Heat Shock Factor 1 to the Heat Shock Protein 70 Promoter in Vivo

We have previously shown that activation of glu-cocorticoid receptor (GR) signaling in stressed cells will cause inhibition of the heat shock re-sponse as mediated by heat shock transcription factor 1 (HSF1). In that work, a full-length human heat shock protein 70 (Hsp70) promoter was used to measure HSF1 transactivity, and the data sug-gested inhibition of HSF1 through the transactiva-tion or transrepressive properties of GR. Here, we show that the inhibitory effect of glucocorticoid agonist (dexamethasone) upon Hsp70 promoter activity is rapid, occurring within 1 h of hormone addition. Moreover, addition of hormone during the first hour of recovery from stress was sufficient to inhibit HSF1. Thus, dexamethasone is able to rap