ABSTRACT
Heat shock transcription factor 1 (HSF-1) activates the transcription of heat shock genes in eukaryotes. Under normal physiological growth conditions, HSF-1 is a monomer. Its transcriptional activity is repressed by constitutive phosphorylation. Upon activation, HSF-1 forms trimers, 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 demonstrated that newly synthesized pre-mRNAs colocalize to the HSF-1 punctate granules after heat shock, suggesting that these granules are sites of transcription. We further present evidence that glycogen synthase kinase 3β (GSK-3β) and extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) participate in the down regulation of HSF-1 transcriptional activity. Transient increases in the expression of GSK-3β facilitate the disappearance of HSF-1 punctate granules and reduce hsp-70 transcription after heat shock. We have also shown that ERK is the priming kinase for GSK-3β. Taken together, these results indicate that GSK-3β and ERK MAPK facilitate the inactivation of activated HSF-1 after heat shock by dispersing HSF-1 from the sites of transcription.
Evaluation of in vitro and in vivo therapeutic antitumor efficacy of transduction of polo‑like kinase 1 and heat shock transcription factor 1 small interfering RNA
