Evidence map›Paper›PMID 29393852›Full record

ArticleeLife2018

Hsf1 and Hsp70 constitute a two-component feedback loop that regulates the yeast heat shock response.

Joanna Krakowiak, Xu Zheng, Nikit Patel, Zoë A Feder, Jayamani Anandhakumar, Kendra Valerius, David S Gross, Ahmad S Khalil, David Pincus

Open access · goldAbstract read
In one paragraph

Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed
6.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

97 citing papers in PubMed, 166 citations in OpenAlex.

  1. Article
  2. Principles and mechanisms of plant acclimation to heat stress.Nature reviews. Molecular cell biology · 2026
    Review
  3. Article
  4. The role of the nucleus in the control of mitochondrial precursor proteins in yeast.Protein science : a publication of the Protein Society · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Ribosome-associated quality control and related mechanisms.Nature structural & molecular biology · 2026
    Review
  9. Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026
    Review
  10. Review
  11. Article
  12. Sarcolipin but not phospholamban responds toFrontiers in physiology · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. A default silencing mechanism restrains stress-induced genes inbioRxiv : the preprint server for biology · 2025
    Article
  18. Review
  19. Article
  20. Article

37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Joanna Krakowiak *Whitehead Institute for Biomedical Research, Cambridge, United States.
Xu Zheng *Whitehead Institute for Biomedical Research, Cambridge, United States.
Nikit Patel *Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, United States.
Zoë A FederWhitehead Institute for Biomedical Research, Cambridge, United States.
Jayamani AnandhakumarDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, United States.
Kendra ValeriusWhitehead Institute for Biomedical Research, Cambridge, United States.
David S GrossDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, United States.
Ahmad S KhalilWhitehead Institute for Biomedical Research, Cambridge, United States.
David PincusWhitehead Institute for Biomedical Research, Cambridge, United States.ORCID http://orcid.org/0000-0002-9651-6858
Whitehead Institute for Biomedical Research · USBoston University · USLouisiana State University Health Sciences Center Shreveport · US

Funding

Combatting antibiotic resistance with synthetic biology technologiesDP2AI131083 · NIAID · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI KHALIL, AHMAD SAMIR · 2016 to 2016
$2.5M
Quantitative approaches to reveal the homeostatic control mechanisms of stress reDP5OD017941 · OD · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI PINCUS, DAVID · 2013 to 2017
$2.4M
NIAID NIH HHS DP2 AI131083NIH HHS DP5 OD017941NIH HHS DP5 OD017941-01
6 · The paper itself

Abstract

Models for regulation of the eukaryotic heat shock response typically invoke a negative feedback loop consisting of the transcriptional activator Hsf1 and a molecular chaperone. Previously we identified Hsp70 as the chaperone responsible for Hsf1 repression and constructed a mathematical model that recapitulated the yeast heat shock response (Zheng et al., 2016). The model was based on two assumptions: dissociation of Hsp70 activates Hsf1, and transcriptional induction of Hsp70 deactivates Hsf1. Here we validate these assumptions. First, we severed the feedback loop by uncoupling Hsp70 expression from Hsf1 regulation. As predicted by the model, Hsf1 was unable to efficiently deactivate in the absence of Hsp70 transcriptional induction. Next, we mapped a discrete Hsp70 binding site on Hsf1 to a C-terminal segment known as conserved element 2 (CE2). In vitro, CE2 binds to Hsp70 with low affinity (9 µM), in agreement with model requirements. In cells, removal of CE2 resulted in increased basal Hsf1 activity and delayed deactivation during heat shock, while tandem repeats of CE2 sped up Hsf1 deactivation. Finally, we uncovered a role for the N-terminal domain of Hsf1 in negatively regulating DNA binding. These results reveal the quantitative control mechanisms underlying the heat shock response.

Indexed as

Feedback, PhysiologicalGene Expression Regulation, FungalHeat-Shock ResponseDNA-Binding ProteinsHeat-Shock ProteinsHSP70 Heat-Shock ProteinsModels, BiologicalModels, TheoreticalSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscription FactorsDNA-Binding ProteinsHeat-Shock ProteinsHSF1 protein, S cerevisiaeHSP70 Heat-Shock ProteinsSaccharomyces cerevisiae ProteinsTranscription Factorsbiochemistrycomputational biologyheat shockHsf1Hsp70S. cerevisiaesystems biology

Identifiers

PMID29393852
PMCPMC5809143
OpenAlexW2750793165

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.