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Molecular and Cellular Biology, November 1998, p. 6624-6633, Vol. 18, No. 11
Institute of Molecular Medicine and Genetics,
Department of Radiology, Medical College of Georgia, Augusta,
Georgia 30912
Received 10 March 1998/Returned for modification 1 June
1998/Accepted 30 July 1998
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 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Glycogen Synthase Kinase 3
and Extracellular Signal-Regulated
Kinase Inactivate Heat Shock Transcription Factor 1 by Facilitating
the Disappearance of Transcriptionally Active Granules after
Heat Shock
(GSK-3
) 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-3
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-3
. Taken together, these results indicate
that GSK-3
and ERK MAPK facilitate the inactivation of activated
HSF-1 after heat shock by dispersing HSF-1 from the sites of
transcription.
*
Corresponding author. Mailing address: Institute of
Molecular Medicine and Genetics, Department of Radiology, Medical
College of Georgia, 1120 15th St., Room CB2803, Augusta, GA 30912. Phone: (706) 721-8759. Fax: (706) 721-8752. E-mail:
mivechi{at}immag.mcg.edu.
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