Yeast Glycogen Synthase Kinase-3 Activates Msn2p-dependent Transcription of Stress Responsive Genes
- 1 January 2003
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 14 (1) , 302-312
- https://doi.org/10.1091/mbc.e02-05-0247
Abstract
The yeast Saccharomyces cerevisiae has four genes,MCK1, MDS1 (RIM11),MRK1, and YOL128c, that encode homologues of mammalian glycogen synthase kinase 3 (GSK-3). A gsk-3null mutant in which these four genes are disrupted showed growth defects on galactose medium. We isolated several multicopy suppressors of this growth defect. Two of them encoded Msn2p and phosphoglucomutase (PGM). Msn2p is a transcription factor that binds to the stress-response element (STRE). PGM is an enzyme that interconverts glucose-1 phosphate and glucose-6 phosphate and is regulated by Msn2p at the transcriptional level. Expression of the mRNAs ofPGM2 and DDR2, whose promoter regions possess STRE sequences, on induction by heat shock or salt stress was reduced not only in an msn2 msn4 (msn2homologue) double mutant but also in the gsk-3 null mutant. STRE-dependent transcription was greatly inhibited in thegsk-3 null mutant or mck1 mds1 double mutant, and this phenotype was suppressed by the expression of Mck1p but not of a kinase-inactive form of Mck1p. Although Msn2p accumulated in the nucleus of the gsk-3 null mutant as well as in the wild-type strain under various stress conditions, its STRE-binding activity was reduced in extracts prepared from the gsk-3null mutant or mck1 mds1 double mutant. These results suggest that yeast GSK-3 promotes formation of a complex between Msn2p and DNA, which is required for the proper response to different forms of stress. Because neither Msn2p–GSK-3 complex formation nor GSK-3–dependent phosphorylation of Msn2p could be detected, the regulation of Msn2p by GSK-3 may be indirect.Keywords
This publication has 44 references indexed in Scilit:
- Direct and Novel Regulation of cAMP-dependent Protein Kinase by Mck1p, a Yeast Glycogen Synthase Kinase-3Published by Elsevier ,2002
- The renaissance of GSK3Nature Reviews Molecular Cell Biology, 2001
- Glycogen synthase kinase 3 regulates cell fate in dictyosteliumCell, 1995
- A family of hexosephosphate mutases in Saccharomyces cerevisiaeEuropean Journal of Biochemistry, 1994
- Mammalian Ras interacts directly with the serine/threonine kinase rafPublished by Elsevier ,1993
- Glycogen synthase kinase-3: functions in oncogenesis and developmentBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1992
- A suppressor of a centromere DNA mutation encodes a putative protein kinase (MCK1).Genes & Development, 1991
- The yeast MCK1 gene encodes a protein kinase homolog that activates early meiotic gene expression.Genes & Development, 1991
- Multiple functions of a Drosophila homeotic gene, zeste-white 3, during segmentation and neurogenesisDevelopmental Biology, 1989
- New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sitesGene, 1988