Protein Kinase A Regulates Constitutive Expression of Small Heat-Shock Genes in an Msn2/4p-Independent and Hsf1p-Dependent Manner in Saccharomyces cerevisiae

Ferguson, Scott B.; Anderson, Erik S.; Harshaw, Robyn B.; Thate, Tim; Craig, Nancy L.; Nelson, Hillary C. M.

doi:10.1534/genetics.104.034256

Cited by 60 publications

(66 citation statements)

References 68 publications

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“…While these have been traditionally thought to physically interact with one or both activation domains, the possibility of alternative or additional mechanisms of repression, including the recruitment of corepressors, has not been ruled out. Recently, a role for protein kinase A in maintaining HSF in a repressed state, at least with respect to its regulation of HSP12 and HSP26, has been reported (Ferguson et al 2005).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to HSP82, the chaperoneencoding genes HSP12, HSP26, HSP104, and SSA4 are regulated by HSF (Halladay and Craig 1995;Lee et al 2002;Ferguson et al 2005). And, as summarized in Table 3, the promoter regions of these genes are occupied by HSF even under noninducing conditions (see also Hahn et al 2004).…”

Section: Resultsmentioning

confidence: 99%

“…And, as summarized in Table 3, the promoter regions of these genes are occupied by HSF even under noninducing conditions (see also Hahn et al 2004). Nonetheless, they exhibit interesting differences in their regulation (e.g., see Ferguson et al 2005), and their transcription might be affected by the ewe suppressors in distinct ways. As shown in Figure 5, basal HSP mRNA levels generally increased in the presence of each ewe mutation.…”

Section: Resultsmentioning

confidence: 99%

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A Functional Module of Yeast Mediator That Governs the Dynamic Range of Heat-Shock Gene Expression

Singh

Erkine²,

Kremer³

et al. 2006

Genetics

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We report the results of a genetic screen designed to identify transcriptional coregulators of yeast heatshock factor (HSF). This sequence-specific activator is required to stimulate both basal and induced transcription; however, the identity of factors that collaborate with HSF in governing noninduced heatshock gene expression is unknown. In an effort to identify these factors, we isolated spontaneous extragenic suppressors of hsp82-DHSE1, an allele of HSP82 that bears a 32-bp deletion of its high-affinity HSF-binding site, yet retains its two low-affinity HSF sites. Nearly 200 suppressors of the null phenotype of hsp82-DHSE1 were isolated and characterized, and they sorted into six expression without heat-shock element (EWE) complementation groups. Strikingly, all six groups contain alleles of genes that encode subunits of Mediator. Three of the six subunits, Med7, Med10/Nut2, and Med21/Srb7, map to Mediator's middle domain; two subunits, Med14/Rgr1 and Med16/Sin4, to its tail domain; and one subunit, Med19/Rox3, to its head domain. Mutations in genes encoding these factors enhance not only the basal transcription of hsp82-DHSE1, but also that of wild-type heat-shock genes. In contrast to their effect on basal transcription, the more severe ewe mutations strongly reduce activated transcription, drastically diminishing the dynamic range of heat-shock gene expression. Notably, targeted deletion of other Mediator subunits, including the negative regulators Cdk8/Srb10, Med5/Nut1, and Med15/Gal11 fail to derepress hsp82-DHSE1. Taken together, our data suggest that the Ewe subunits constitute a distinct functional module within Mediator that modulates both basal and induced heat-shock gene transcription. W HEN exposed to thermal or chemical stress, organisms respond by vigorously transcribing genes encoding heat-shock proteins (HSPs). HSPs function as molecular chaperones and protect the cellalong with ubiquitin, proteases, metallothioneins, and antioxidant enzymes-from damage caused by the expression of misfolded proteins. In the yeast Saccharomyces cerevisiae, the expression of heat-responsive genes is stimulated by the sequence-specific transcriptional activator heat-shock factor (HSF) Hsf1 (ScHSF) (Sorger and Pelham 1988;Nieto-Sotelo et al. 1990;Sorger 1990). In response to metabolic, oxidative, or osmotic stress, the transcription of a number of HSP genes is additionally enhanced by the gene-specific activators Msn2/Msn4 and Skn7 (Boy-Marcotte et al. 1998;Treger et al. 1998;Gasch et al. 2000;Raitt et al. 2000;Amoros and Estruch 2001;Kandror et al. 2004). Nonetheless, the only activator known to promote basal heat-shock gene transcription is HSF (McDaniel et al. 1989;Park and Craig 1989;Erkine et al. 1996). Whether this basal expression is an indirect consequence of HSF's role in establishing and maintaining a nucleosomeremodeled (''nucleosome-free'') structure over the transcription start site Erkine et al. 1996), or whether HSF plays a more direct role in recruiting transcriptional coactivators under n...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A Functional Module of Yeast Mediator That Governs the Dynamic Range of Heat-Shock Gene Expression

Singh

Erkine²,

Kremer³

et al. 2006

Genetics

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“…Since the YAK1 gene itself is induced by Msn2/4, this would generate a positive feedback loop (Smith et al 1998). In the same study, Yak1 was also found to stimulate the activity of Hsf1, another transcriptional activator of stress response genes that was recently shown to be under negative control of PKA (Hahn et al 2004;Ferguson et al 2005;Lee et al 2008a). Rim15 was initially identified as an activator of meiotic gene expression (Vidan and Mitchell 1997).…”

Section: Regulation Of the Camp-pka Pathwaymentioning

confidence: 93%

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

et al. 2010

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Cells of all living organisms contain complex signal transduction networks to ensure that a wide range of physiological properties are properly adapted to the environmental conditions. The fundamental concepts and individual building blocks of these signalling networks are generally well-conserved from yeast to man; yet, the central role that growth factors and hormones play in the regulation of signalling cascades in higher eukaryotes is executed by nutrients in yeast. Several nutrient-controlled pathways, which regulate cell growth and proliferation, metabolism and stress resistance, have been defined in yeast. These pathways are integrated into a signalling network, which ensures that yeast cells enter a quiescent, resting phase (G 0 ) to survive periods of nutrient scarceness and that they rapidly resume growth and cell proliferation when nutrient conditions become favourable again. A series of well-conserved nutrient-sensory protein kinases perform key roles in this signalling network: i.e. Snf1, PKA, Tor1 and Tor2, Sch9 and Pho85-Pho80. In this review, we provide a comprehensive overview on the current understanding of the signalling processes mediated via these kinases with a particular focus on how these individual pathways converge to signalling networks that ultimately ensure the dynamic translation of extracellular nutrient signals into appropriate physiological responses.

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“…Phosphorylation of mammalian HSF1 is implicated in both positive and negative regulation of the activator function, but the mechanistic details of this regulation are incompletely understood (23,24). S. cerevisiae Hsf1 is constitutively phosphorylated and is presumably controlled in a negative manner by the cAMP-dependent kinase (25). Further phosphorylation by the AMP-activated kinase Snf1 is required for glucose starvation-induced transcription mediated by Hsf1 (19).…”

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confidence: 99%

Mutated Yeast Heat Shock Transcription Factor Activates Transcription Independently of Hyperphosphorylation

Hashikawa¹,

Mizukami

Imazu

et al. 2006

Journal of Biological Chemistry

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The homotrimeric heat shock transcription factor (HSF) binds to the heat shock element of target genes and regulates transcription in response to various stresses. The Hsf1 protein of Saccharomyces cerevisiae is extensively phosphorylated upon heat shock; a modification that is under positive regulation by its C-terminal regulatory domain (CTM). Hyperphosphorylation has been implicated in gene-specific transcriptional activation. Here, we surveyed genes whose heat shock response is reduced by a CTM mutation. The CTM is indispensable for transcription via heat shock elements bound by a single Hsf1 trimer but is dispensable for transcription via heat shock elements bound by Hsf1 trimers in a cooperative manner. Intragenic mutations located within or near the wing region of the winged helix-turn-helix DNA-binding domain suppress the temperature-sensitive growth phenotype associated with the CTM mutation and enable Hsf1 to activate transcription independently of hyperphosphorylation. Deletion of the wing partially restores the transcriptional defects of the unphosphorylated Hsf1. These results demonstrate a functional link between hyperphosphorylation and the wing region and suggest that this modification is involved in a conformational change of a single Hsf1 trimer to an active form.The eukaryotic heat shock transcription factor HSF regulates the transcription of various genes under numerous stressful conditions. HSF proteins share common structural motifs, including a winged helix-turn-helix DNA-binding domain (DBD), 3 a hydrophobic repeat region essential for three-stranded coiled-coil formation, and a C-terminal transactivation domain (1-3). HSF binds to a conserved DNA sequence motif termed the heat shock element (HSE) by forming a homotrimer through the hydrophobic repeat regions, and the DBD of each monomer recognizes a 5-bp sequence, 5Ј-nGAAn-3Ј. The organization of the three nGAAn units varies among functional HSEs (4 -13). The perfect-type HSE consists of three or more contiguous inverted repeats of the unit (nTTCnnGAAnnTTCn), the gap-type HSE consists of two inverted units separated from a third unit by a 5-bp gap (nTTCnnGAAn(5 bp)nGAAn), and the step-type HSE consists of direct repeats of the nGAAn or nTTCn motif separated by 5 bp (nGAAn(5 bp)nGAAn(5 bp)nGAAn).In the yeast Saccharomyces cerevisiae, the HSF encoded by the HSF1 gene regulates transcription under normal physiological conditions as well as under stress conditions, and it is essential for cell viability. The genes targeted by Hsf1 encode proteins that function in a broad range of biological processes, including protein folding and degradation, detoxification, energy generation, carbohydrate metabolism, and cell wall organization (12, 13). Mammalian cells contain three HSF isoforms, HSF1, HSF2, and HSF4. Among these, HSF1 has roles in stress-induced transcription, extra-embryonic development, and postnatal growth (14, 15). Both S. cerevisiae Hsf1 and mammalian HSF1 are inducibly phosphorylated concomitant with activation (16 -22). Phosphoryla...

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Protein Kinase A Regulates Constitutive Expression of Small Heat-Shock Genes in an Msn2/4p-Independent and Hsf1p-Dependent Manner in Saccharomyces cerevisiae

Cited by 60 publications

References 68 publications

A Functional Module of Yeast Mediator That Governs the Dynamic Range of Heat-Shock Gene Expression

A Functional Module of Yeast Mediator That Governs the Dynamic Range of Heat-Shock Gene Expression

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

Mutated Yeast Heat Shock Transcription Factor Activates Transcription Independently of Hyperphosphorylation

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