Activation of the Saccharomyces cerevisiae heat shock transcription factor under glucose starvation conditions by Snf1 protein kinase.
Heat shock transcription factor (HSF) is an evolutionarily conserved protein that mediates eukaryotic transcriptional responses to stress. Although the mammalian stress-responsive HSF1 isoform is activated in response to a wide array of seemingly unrelated stresses, including heat shock, pharmacological agents, infection and inflammation, little is known about the precise mechanisms or pathways by which this factor is activated by many stressors. The baker's yeast Saccharomyces cerevisiae encodes a single HSF protein that responds to heat stress and glucose starvation and provides a simple model system to investigate how a single HSF is activated by multiple stresses. Although induction of the HSF target gene CUP1 by glucose starvation is dependent on the Snf1 kinase, HSF-dependent heat shock induction of CUP1 is Snf1-independent. Approximately 165 in vivo targets for HSF have been identified in S. cerevisiae using chromatin immunoprecipitation combined with DNA microarrays. Interestingly, approximately 30% of the HSF direct target genes are also induced by the diauxic shift, in which glucose levels begin to be depleted. We demonstrate that HSF and Snf1 kinase interact in vivo and that HSF is a direct substrate for phosphorylation by Snf1 kinase in vitro. Furthermore, glucose starvation-dependent, but not heat shock-dependent HSF phosphorylation, and enhanced chromosomal HSF DNA binding to low affinity target promoters such as SSA3 and HSP30, occurred in a Snf1-dependent manner. Consistent with a more global role for HSF and Snf1 in activating gene expression in response to changes in glucose availability, expression of a subset of HSF targets by glucose starvation was dependent on Snf1 and the HSF carboxyl-terminal activation domain.
Hahn
Ji-Sook
JS
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109-0606, USA.
Thiele
Dennis J
DJ
D002244:Carbon / Q000378:metabolism; D002352:Carrier Proteins; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry*; D015151:Immunoblotting; D008668:Metallothionein / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000378:metabolism
C500769:CUP1-1 protein, S cerevisiae; D002352:Carrier Proteins; D002843:Chromatin; D006360:Heat-Shock Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; C007121:copper thionein; D002244:Carbon; D004247:DNA; D008668:Metallothionein; D005982:Glutathione Transferase; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D001616:beta-Galactosidase; D005947:Glucose