Evidence map›Paper›PMID 27354066›Full record

ArticleMolecular and cellular biology2016

Heat Shock Factor 1 Is a Substrate for p38 Mitogen-Activated Protein Kinases.

Sharadha Dayalan Naidu, Calum Sutherland, Ying Zhang, Ana Risco, Laureano de la Vega, Christopher J Caunt, C James Hastie, Douglas J Lamont, Laura Torrente, Sudhir Chowdhry and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. HSF1 Activation Mechanisms, Disease Roles, and Small Molecule Therapeutics.International journal of biological sciences · 2025
    Review
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  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
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  14. Review
  15. Article
  16. Article
  17. Heat Shock Proteins and HSF1 in Cancer.Frontiers in oncology · 2022
    Review
  18. Article
  19. Article
  20. Article
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

14 authors at 5 institutions in 3 countries.

Sharadha Dayalan NaiduDivision of Cancer Research, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom.
Calum SutherlandDivision of Cardiovascular and Diabetes Medicine, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom.
Ying ZhangDivision of Cancer Research, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom.
Ana RiscoDepartment of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.
Laureano de la VegaDivision of Cancer Research, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom.
Christopher J CauntDepartment of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom.
C James HastieDivision of Signal Transduction Therapy, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom.
Douglas J LamontDivision of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom.
Laura TorrenteDivision of Cancer Research, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom.
Sudhir ChowdhryDivision of Cancer Research, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom.
Ivor J BenjaminCardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Stephen M KeyseDivision of Cancer Research, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom.
Ana CuendaDepartment of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.
Albena T Dinkova-KostovaDivision of Cancer Research, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom Department of Pharmacology and Molecular Sciences and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA a.dinkovakostova@dundee.ac.uk.
University of Dundee · GBCentro Nacional de Biotecnología · ESJohns Hopkins University · USMedical College of Wisconsin · USUniversity of Bath · GB

Funding

Biotechnology and Biological Sciences Research Council BB/J007498/1
6 · The paper itself

Abstract

Heat shock factor 1 (HSF1) monitors the structural integrity of the proteome. Phosphorylation at S326 is a hallmark for HSF1 activation, but the identity of the kinase(s) phosphorylating this site has remained elusive. We show here that the dietary agent phenethyl isothiocyanate (PEITC) inhibits heat shock protein 90 (Hsp90), the main negative regulator of HSF1; activates p38 mitogen-activated protein kinase (MAPK); and increases S326 phosphorylation, trimerization, and nuclear translocation of HSF1, and the transcription of a luciferase reporter, as well as the endogenous prototypic HSF1 target Hsp70. In vitro, all members of the p38 MAPK family rapidly and stoichiometrically catalyze the S326 phosphorylation. The use of stable knockdown cell lines and inhibitors indicated that among the p38 MAPKs, p38γ is the principal isoform responsible for the phosphorylation of HSF1 at S326 in cells. A protease-mass spectrometry approach confirmed S326 phosphorylation and unexpectedly revealed that p38 MAPK also catalyzes the phosphorylation of HSF1 at S303/307, previously known repressive posttranslational modifications. Thus, we have identified p38 MAPKs as highly efficient catalysts for the phosphorylation of HSF1. Furthermore, our findings suggest that the magnitude and persistence of activation of p38 MAPK are important determinants of the extent and duration of the heat shock response.

Indexed as

Transcription, GeneticAnimalsCell LineDNA-Binding ProteinsHeat Shock Transcription FactorsHeLa CellsHSP70 Heat-Shock ProteinsHSP90 Heat-Shock ProteinsHumansIsothiocyanatesMiceMouse Embryonic Stem Cellsp38 Mitogen-Activated Protein KinasesPhosphorylationProtein MultimerizationProtein TransportDNA-Binding ProteinsHeat Shock Transcription FactorsHSF1 protein, humanHSP70 Heat-Shock ProteinsHSP90 Heat-Shock ProteinsIsothiocyanatesp38 Mitogen-Activated Protein Kinasesphenethyl isothiocyanateSerineTranscription Factors

Identifiers

PMID27354066
PMCPMC5007788
OpenAlexW2471550966

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.