GLYCOGEN-SYNTHASE KINASE 3-BETA AND EXTRACELLULAR SIGNAL-REGULATED KINASE INACTIVATE HEAT-SHOCK TRANSCRIPTION FACTOR-1 BY FACILITATING THE DISAPPEARANCE OF TRANSCRIPTIONALLY ACTIVE GRANULES AFTER HEAT-SHOCK

Heat shock transcription factor 1 (HSF-1) activates the transcription of heat shock genes in eukaryotes. Under normal physiological growth c onditions, HSF-1 is a monomer. Its transcriptional activity is repress ed by constitutive phosphorylation. Upon activation, HSF-1 forms trime rs, acquires DNA binding activity, increases transcriptional activity, and appears as punctate granules in the nucleus. In this study, using bromouridine incorporation and confocal laser microscopy, we demonstr ated that newly synthesized pre-mRNAs colocalize to the HSF-1 punctate granules after heat shock, suggesting that these granules are sites o f transcription. We further present evidence that glycogen synthase ki nase 3 beta (GSK-3 beta) and extracellular signal-regulated kinase mit ogen-activated protein kinase (ERK MAPK) participate in the down regul ation of HSF-1 transcriptional activity. Transient increases in the ex pression of GSK-3 beta facilitate the disappearance of HSF-1 punctate granules and reduce hsp-70 transcription after heat shock. We have als o shown that ERK is the priming kinase for GSK-3 beta. Taken together, these results indicate that GSK-3 beta and ERK MAPK facilitate the in activation of activated HSF-1 after heat shock by dispersing HSF-1 fro m the sites of transcription.