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 previous studies, we showed that HSF 1 is phosphorylated by the protein kinase RSK2 in vitro and that this effect is inhibited by nonsteroidal anti-inflammatory drugs at the concentration that leads to the activation of HSF1 in vivo (Stevenson et al 1999). In the present study, using cells from a patient with Coffin-Lowry syndrome (deficient in RSK2), we demonstrate that RSK2 slightly represses activation of HSF1 in vivo at 37 degrees C. In Coffin-Lowry syndrome cells, HSF1-HSE DNA binding activity after treatment with sodium salicylate was slightly higher than that in untreated cells, indicating that although RSK2 is involved in HSF1 regulation, it is not the unique protein kinase that suppresses HSF1-HSE binding activity at 37 degrees C. However, heat shock treatment resulted in significantly higher HSF1-HSE binding activity in Coffin-Lowry syndrome cells as compared with normal controls, suggesting that RSK2 represses HSF1-HSE binding activity during heat shock.
Wang
X
X
Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Asea
A
A
Xie
Y
Y
Kabingu
E
E
Stevenson
M A
MA
Calderwood
S K
SK
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology; D008297:Male; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012980:Sodium Salicylate / Q000494:pharmacology; D014157:Transcription Factors; D014162:Transfection
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D019893:Ribosomal Protein S6 Kinases; D012980:Sodium Salicylate