Identification of cis and trans components of a novel heat shock stress regulatory pathway in Saccharomyces cerevisiae.

The stress-responsive DDR2 gene (previously called DDRA2) of Saccharomyces cerevisiae is transcribed at elevated levels following stress caused by heat shock or DNA damage. Previously, we identified a 51-bp promoter fragment, oligo31/32, which conferred heat shock inducibility on the heterologous CYC1-lacZ reporter gene in S. cerevisiae (N. Kobayashi and K. McEntee, Proc. Natl. Acad. Sci. USA 87:6550-6554, 1990). Using a series of synthetic oligonucleotides, we have identified a pentanucleotide, CCCCT (C4T), as an essential component of this stress response sequence. This element is not a binding site for the well-characterized heat shock transcription factor which recognizes a distinct cis-acting heat shock element in the promoters of many heat shock genes. Here we demonstrate the ability of oligonucleotides containing the C4T sequence to confer heat shock inducibility on the reporter gene and show that the presence of two such elements produces more than additive effects on induction. Gel retardation experiments have been used to demonstrate specific complex formation between C4T-containing fragments and one or more yeast proteins. Formation of these complexes was not competed by fragments containing mutations in the C4T sequence nor by heat shock element-containing competitor DNAs. Fragments containing the C4T element bound to a single 140-kDa polypeptide, distinct from heat shock transcription factors in yeast crude extracts. These experiments identify key cis- and trans-acting components of a novel heat shock stress response pathway in S. cerevisiae.

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hsc70 moderates the heat shock (stress) response in Xenopus laevis oocytes and binds to denatured protein inducers.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)40740-x ◽

1994 ◽

Vol 269 (22) ◽

pp. 15718-15723 ◽

Cited By ~ 2

Author(s):

L.C. Mifflin ◽

R.E. Cohen

Keyword(s):

Stress Response ◽

Heat Shock ◽

Xenopus Laevis ◽

Xenopus Laevis Oocytes ◽

Denatured Protein ◽

Heat Shock Stress ◽

Shock Stress

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Direct link between metabolic regulation and the heat-shock response through the transcriptional regulator PGC-1α

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1516219112 ◽

2015 ◽

Vol 112 (42) ◽

pp. E5669-E5678 ◽

Cited By ~ 26

Author(s):

Neri Minsky ◽

Robert G. Roeder

Keyword(s):

Gene Expression ◽

Stress Response ◽

Heat Shock ◽

Metabolic Regulation ◽

Hormone Receptors ◽

Transcriptional Networks ◽

Direct Link ◽

Heat Shock Stress ◽

Metabolic Genes ◽

Shock Stress

In recent years an extensive effort has been made to elucidate the molecular pathways involved in metabolic signaling in health and disease. Here we show, surprisingly, that metabolic regulation and the heat-shock/stress response are directly linked. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a critical transcriptional coactivator of metabolic genes, acts as a direct transcriptional repressor of heat-shock factor 1 (HSF1), a key regulator of the heat-shock/stress response. Our findings reveal that heat-shock protein (HSP) gene expression is suppressed during fasting in mouse liver and in primary hepatocytes dependent on PGC-1α. HSF1 and PGC-1α associate physically and are colocalized on several HSP promoters. These observations are extended to several cancer cell lines in which PGC-1α is shown to repress the ability of HSF1 to activate gene-expression programs necessary for cancer survival. Our study reveals a surprising direct link between two major cellular transcriptional networks, highlighting a previously unrecognized facet of the activity of the central metabolic regulator PGC-1α beyond its well-established ability to boost metabolic genes via its interactions with nuclear hormone receptors and nuclear respiratory factors. Our data point to PGC-1α as a critical repressor of HSF1-mediated transcriptional programs, a finding with possible implications both for our understanding of the full scope of metabolically regulated target genes in vivo and, conceivably, for therapeutics.

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The Heat Shock/Stress Response after Ischemia

Primer on Cerebrovascular Diseases ◽

10.1016/b978-012743170-3/50068-6 ◽

1997 ◽

pp. 234-236

Author(s):

T NOWAKJR

Keyword(s):

Stress Response ◽

Heat Shock ◽

Heat Shock Stress ◽

Shock Stress

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The Heat Shock/Stress Response after Ischemia

Primer on Cerebrovascular Diseases ◽

10.1016/b978-012743170-3.50068-6 ◽

1997 ◽

pp. 234-236

Author(s):

Thaddeus S. Nowak

Keyword(s):

Stress Response ◽

Heat Shock ◽

Heat Shock Stress ◽

Shock Stress

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Association of Constitutive Hyperphosphorylation of Hsf1p with a Defective Ethanol Stress Response in Saccharomyces cerevisiae Sake Yeast Strains

Applied and Environmental Microbiology ◽

10.1128/aem.06341-11 ◽

2011 ◽

Vol 78 (2) ◽

pp. 385-392 ◽

Cited By ~ 18

Author(s):

Chiemi Noguchi ◽

Daisuke Watanabe ◽

Yan Zhou ◽

Takeshi Akao ◽

Hitoshi Shimoi

Keyword(s):

Saccharomyces Cerevisiae ◽

Stress Response ◽

Heat Shock ◽

Laboratory Strain ◽

Underlying Mechanism ◽

Ethanol Stress ◽

Heat Shock Element ◽

Content Type ◽

Yeast Strains ◽

Acute Ethanol

ABSTRACTModern sake yeast strains, which produce high concentrations of ethanol, are unexpectedly sensitive to environmental stress during sake brewing. To reveal the underlying mechanism, we investigated a well-characterized yeast stress response mediated by a heat shock element (HSE) and heat shock transcription factor Hsf1p inSaccharomyces cerevisiaesake yeast. The HSE-lacZactivity of sake yeast during sake fermentation and under acute ethanol stress was severely impaired compared to that of laboratory yeast. Moreover, the Hsf1p of modern sake yeast was highly and constitutively hyperphosphorylated, irrespective of the extracellular stress. SinceHSF1allele replacement did not significantly affect the HSE-mediated ethanol stress response or Hsf1p phosphorylation patterns in either sake or laboratory yeast, the regulatory machinery of Hsf1p is presumed to function differently between these types of yeast. To identify phosphatases whose loss affected the control of Hsf1p, we screened a series of phosphatase gene deletion mutants in a laboratory strain background. Among the 29 mutants, a Δppt1mutant exhibited constitutive hyperphosphorylation of Hsf1p, similarly to the modern sake yeast strains, which lack the entirePPT1gene locus. We confirmed that the expression of laboratory yeast-derived functionalPPT1recovered the HSE-mediated stress response of sake yeast. In addition, deletion ofPPT1in laboratory yeast resulted in enhanced fermentation ability. Taken together, these data demonstrate that hyperphosphorylation of Hsf1p caused by loss of thePPT1gene at least partly accounts for the defective stress response and high ethanol productivity of modern sake yeast strains.

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A bipartite operator interacts with a heat shock element to mediate early meiotic induction of Saccharomyces cerevisiae HSP82.

Molecular and Cellular Biology ◽

10.1128/mcb.15.12.6754 ◽

1995 ◽

Vol 15 (12) ◽

pp. 6754-6769 ◽

Cited By ~ 23

Author(s):

C Szent-Gyorgyi

Keyword(s):

Saccharomyces Cerevisiae ◽

Heat Shock ◽

Point Mutations ◽

Early Step ◽

Heat Shock Element ◽

Cis Acting ◽

Major Mode ◽

Dna Elements ◽

Insight Into ◽

Activation Sequence

Although key genetic regulators of early meiotic transcription in Saccharomyces cerevisiae have been well characterized, the activation of meiotic genes is still poorly understood in terms of cis-acting DNA elements and their associated factors. I report here that induction of HSP82 is regulated by the early meiotic IME1-IME2 transcriptional cascade. Vegetative repression and meiotic induction depend on interactions of the promoter-proximal heat shock element (HSE) with a nearby bipartite repression element, composed of the ubiquitous early meiotic motif, URS1 (upstream repression sequence 1), and a novel ancillary repression element. The ancillary repression element is required for efficient vegetative repression, is spatially separable from URS1, and continues to facilitate repression during sporulation. In contrast, URS1 also functions as a vegetative repression element but is converted early in meiosis into an HSE-dependent activation element. An early step in this transformation may be the antagonism of URS1-mediated repression by IME1. The HSE also nonspecifically supports a second major mode of meiotic activation that does not require URS1 but does require expression of IME2 and concurrent starvation. Interestingly, increased rather than decreased URS1-mediated vegetative transcription can be artificially achieved by introducing rare point mutations into URS1 or by deleting the UME6 gene. These lesions offer insight into mechanisms of URS-dependent repression and activation. Experiments suggest that URS1-bound factors functionally modulate heat shock factor during vegetative transcription and early meiotic induction but not during heat shock. The loss of repression and activation observed when the IME2 activation element, T4C, is substituted for the HSE suggests specific requirements for URS1-upstream activation sequence interactions.

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Protein Expression Profiles of Chlamydia pneumoniae in Models of Persistence versus Those of Heat Shock Stress Response

Infection and Immunity ◽

10.1128/iai.02104-05 ◽

2006 ◽

Vol 74 (7) ◽

pp. 3853-3863 ◽

Cited By ~ 36

Author(s):

Sanghamitra Mukhopadhyay ◽

Richard D. Miller ◽

Erin D. Sullivan ◽

Christina Theodoropoulos ◽

Sarah A. Mathews ◽

...

Keyword(s):

Stress Response ◽

Heat Shock ◽

Protein Expression ◽

Chlamydia Pneumoniae ◽

Expression Profiles ◽

Stress Component ◽

Expression Patterns ◽

Heat Shock Stress ◽

Shock Stress

ABSTRACT Chlamydia pneumoniae is an obligate intracellular pathogen that causes both acute and chronic human disease. Several in vitro models of chlamydial persistence have been established to mimic chlamydial persistence in vivo. We determined the expression patterns of 52 C. pneumoniae proteins, representing nine functional subgroups, from the gamma interferon (IFN-γ) treatment (primarily tryptophan limitation) and iron limitation (IL) models of persistence compared to those following heat shock (HS) at 42°C. Protein expression patterns of C. pneumoniae persistence indicates a strong stress component, as evidenced by the upregulation of proteins involved in protein folding, assembly, and modification. However, it is clearly more than just a stress response. In IFN persistence, but not IL or HS, amino acid and/or nucleotide biosynthesis proteins were found to be significantly upregulated. In contrast, proteins involved in the biosynthesis of cofactors, cellular processes, energy metabolism, transcription, and translation showed an increased in expression in only the IL model of persistence. These data represent the most extensive protein expression study of C. pneumoniae comparing the chlamydial heat shock stress response to two models of persistence and identifying the common and unique protein level responses during persistence.

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