RSK2 represses HSF1 activation during heat shock

Heat shock transcription factor 1(HSF1) activation is a multistep process. The conversion of a latent cytoplasmic form to a nuclear, DNA binding state appears to be activated by nonsteroidal anti-inflammatory drugs. in previo us studies, we showed that HSF 1 is phosphorylated by the protein kinase RS K2 in vitro and that this effect is inhibited by nonsteroidal anti-inflamma tory drugs at the concentration that leads to the activation of HSF1 in viv o (Stevenson et at 1999). In the present study, using cells from a patient with Coffin-Lowry syndrome (deficient in RSK2), we demonstrate that RSK2 sl ightly represses activation of HSF1 in vivo at 37 degreesC. in Coffin-Lowry syndrome cells, HSF1-HSE DNA binding activity after treatment with sodium salicylate was slightly higher than that in untreated cells, indicating tha t although RSK2 is involved in HSF1 regulation, it is not the unique protei n kinase that suppresses HSF1-HSE binding activity at 37 degreesC. However, heat shock treatment resulted in significantly higher HSF1-HSE binding act ivity in Coffin-Lowly syndrome cells as compared with normal controls, sugg esting that RSK2 represses HSF1-HSE binding activity during heat shock.