In the yeast heat shock response, Hsf1-directed induction of Hsp90 facilitates the activation of the Slt2 (Mpk1) mitogen-activated protein kinase required for cell integrity

Truman, Andrew W, Millson, Stefan H, Nuttall, James M, Mollapour, Mehdi, Prodromou, Chrisostomos and Piper, Peter W (2007) In the yeast heat shock response, Hsf1-directed induction of Hsp90 facilitates the activation of the Slt2 (Mpk1) mitogen-activated protein kinase required for cell integrity. Eukaryotic Cell, 6 (4). pp. 744-752. ISSN 1535-9778

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Yeast is rendered temperature sensitive with loss of the C-terminal (CT) domain of heat shock transcription factor (Hsf1). This domain loss was found to abrogate heat stimulation of Slt2 (Mpk1), the mitogen-activated protein kinase that directs the reinforced cell integrity gene expression needed for high-temperature growth. In Hsf1 CT domain-deficient cells, Slt2 still undergoes Mkk1/2-directed dual-Thr/Tyr phosphorylation in response to the heat stimulation of cell integrity pathway signaling, but the low Hsp90 expression level suppresses any corresponding increase in Slt2 kinase activity due to Slt2 being a "client" of the Hsp90 chaperone. A non-Hsf1-directed Hsp90 overexpression restored the heat induction of Slt2 activity in these cells, as well as both Slt2-dependent (Rlm1, Swi4) and Slt2-independent (MBF) transcriptional activities. Their high-temperature growth was also rescued, not just by this Hsp90 overexpression but by osmotic stabilization, by the expression of a Slt2-independent form of the Rlm1 transcriptional regulator of cell integrity genes, and by a multicopy SLT2 gene vector. In providing the elevated Hsp90 needed for an efficient activation of Slt2, heat activation of Hsf1 indirectly facilitates (Slt2-directed) heat activation of yet another transcription factor (Rlm1). This provides an explanation as to why, in earlier transcript analysis compared to chromatin immunoprecipitation studies, many more genes of yeast displayed an Hsf1-dependent transcriptional activation by heat than bound Hsf1 directly. The levels of Hsp90 expression affecting transcription factor regulation by Hsp90 client protein kinases also provides a mechanistic model for how heat shock factor can influence the expression of several non-hsp genes in higher organisms.

Item Type: Article
Keywords: DNA-Binding Proteins/*metabolism Enzyme Activation/drug effects HSP90 Heat-Shock Proteins/*metabolism Heat-Shock Proteins/*metabolism *Heat-Shock Response/drug effects MADS Domain Proteins MAP Kinase Kinase 1/metabolism Macrolides/pharmacology Mitogen-Activated Protein Kinases/*metabolism Mutant Proteins/metabolism Phosphorylation/drug effects Protein Structure, Tertiary/drug effects Saccharomyces cerevisiae/*cytology/drug effects/enzymology/growth & development Saccharomyces cerevisiae Proteins/*metabolism Temperature Transcription Factors/*metabolism Transcription, Genetic/drug effects
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
Depositing User: Chrisostomos Prodromou
Date Deposited: 24 Feb 2015 15:37
Last Modified: 02 Jul 2019 22:46

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