Glycogen synthase kinase 3beta 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 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 3beta (GSK-3beta) 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-3beta 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-3beta. Taken together, these results indicate that GSK-3beta and ERK MAPK facilitate the inactivation of activated HSF-1 after heat shock by dispersing HSF-1 from the sites of transcription.
He
B
B
Institute of Molecular Medicine and Genetics, Department of Radiology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Meng
Y H
YH
Mivechi
N F
NF
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D005455:Fluorescent Antibody Technique; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013696:Temperature; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection / Q000235:genetics
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D009687:Nuclear Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D014157:Transcription Factors; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3