Role of an α-helical bulge in the yeast heat shock transcription factor 1 1Edited by F. E. Cohen

Hardy, James L.; Walsh, Scott T. R.; Nelson, Hillary C. M.

doi:10.1006/jmbi.1999.3357

Cited by 29 publications

(25 citation statements)

References 78 publications

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“…The DBD determines HSE binding specificity, and mutations of amino acids in this region cause gene-specific transcriptional changes (42)(43)(44)(45). The DBD negatively regulates the transcriptional activity of Hsf1 under normal growth conditions (46 -50), and it can directly sense heat shock and undergo conformational changes (48). These observations have highlighted the essential regulatory function of the DBD for gene-specific, heat-inducible transcription.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…More recent studies suggest that the transcriptional activation domains of HSF are in a dynamic association with the DNA-binding and oligomerization domains (Bulman et al 2001;Chen and Parker 2002). Maintaining such domain-domain interactions is important for preserving HSF in a repressive state under normal growth conditions (Hardy et al 2000;Chen and Parker 2002) Figure 6.-The effect of hsf1 alleles on the expression of molecular chaperones. (A) Isogenic DNTA-HSF, DCTA-HSF, and wt-HSF cells were grown in YPD to OD 600 ¼ 0.5.…”

Section: Discussionmentioning

confidence: 99%

De Novo Appearance and “Strain” Formation of Yeast Prion [PSI+] Are Regulated by the Heat-Shock Transcription Factor

et al. 2006

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Yeast prions are non-Mendelian genetic elements that are conferred by altered and self-propagating protein conformations. Such a protein conformation-based transmission is similar to that of PrP Sc , the infectious protein responsible for prion diseases. Despite recent progress in understanding the molecular nature and epigenetic transmission of prions, the underlying mechanisms governing prion conformational switch and determining prion ''strains'' are not understood. We report here that the evolutionarily conserved heat-shock transcription factor (HSF) strongly influences yeast prion formation and strain determination. An hsf1 mutant lacking the amino-terminal activation domain inhibits the yeast prion ] strains, they are capable of receiving and faithfully propagating nonpreferable strains, suggesting that prion initiation and propagation are distinct processes requiring different cellular components. Our findings establish the importance of HSF in prion initiation and strain determination and imply a similar regulatory role of mammalian HSFs in the complex etiology of prion disease.

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“…A notable difference, however, is that HSF is multimerized and activated upon heat shock; whereas TlpA becomes unfolded and inactivated upon shift to elevated temperatures. Intriguingly the yeast HSF DBD was recently shown to affect transcriptional activation in vivo through a proposed mechanism involving changes in the structure of the DBD upon heat stress (Hardy et al 2000). Yeast strains expressing HSF mutants that removed a conserved helical bulge in ␣-helix 2 of HSF exhibited improved survival at nonpermissive temperatures and increased thermotolerance against lethal heat shock, which correlated with higher basal levels of transcriptional activity, compared with cells expressing wild-type HSF.…”

Section: Discussionmentioning

confidence: 99%

The loop domain of heat shock transcription factor 1 dictates DNA-binding specificity and responses to heat stress

Ahn

Liu

Klyachko³

et al. 2001

Genes Dev.

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Eukaryotic heat shock transcription factors (HSF) regulate an evolutionarily conserved stress-response pathway essential for survival against a variety of environmental and developmental stresses. Although the highly similar HSF family members have distinct roles in responding to stress and activating target gene expression, the mechanisms that govern these roles are unknown. Here we identify a loop within the HSF1 DNA-binding domain that dictates HSF isoform specific DNA binding in vitro and preferential target gene activation by HSF family members in both a yeast transcription assay and in mammalian cells. These characteristics of the HSF1 loop region are transposable to HSF2 and sufficient to confer DNA-binding specificity, heat shock inducible HSP gene expression and protection from heat-induced apoptosis in vivo. In addition, the loop suppresses formation of the HSF1 trimer under basal conditions and is required for heat-inducible trimerization in a purified system in vitro, suggesting that this domain is a critical part of the HSF1 heat-stress-sensing mechanism. We propose that this domain defines a signature for HSF1 that constitutes an important determinant for how cells utilize a family of transcription factors to respond to distinct stresses.

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Role of an α-helical bulge in the yeast heat shock transcription factor 1 1Edited by F. E. Cohen

Cited by 29 publications

References 78 publications

Mutated Yeast Heat Shock Transcription Factor Activates Transcription Independently of Hyperphosphorylation

Mutated Yeast Heat Shock Transcription Factor Activates Transcription Independently of Hyperphosphorylation

De Novo Appearance and “Strain” Formation of Yeast Prion [PSI+] Are Regulated by the Heat-Shock Transcription Factor

The loop domain of heat shock transcription factor 1 dictates DNA-binding specificity and responses to heat stress

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