Eukaryotic Cell doi:10.1128/EC.00009-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
In the yeast heat shock response Hsf1-directed induction of Hsp90 facilitates the activation of the Slt2(Mpk1) cell integrity MAP kinase
Andrew W. Truman,
Stefan H. Millson,
James M. Nuttall,
Mehdi Mollapour,
Chrisostomos Prodromou,
and
Peter W. Piper*
Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN and; Section for Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, U.K.
* To whom correspondence should be addressed. Email:
Peter.Piper{at}sheffield.ac.uk.
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Abstract |
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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 (MAPK) 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 as compared to chromatin immunoprecipitation studies - many more genes of yeast displayed a 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.
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