ArticleMolecular and cellular biology2016
Heat Shock Factor 1 Is a Substrate for p38 Mitogen-Activated Protein Kinases.
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.
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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.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Effect of Acupuncture on the p38 Signaling Pathway in Several Nervous System Diseases: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Trial
- Enhancement of colorectal cancer therapy through interruption of the HSF1-HSP90 axis by p53 activation or cell cycle inhibition.Cell death and differentiation · 2025Article
- Targeting the host transcription factor HSF1 prevents human cytomegalovirus replication in vitro and in vivo.Antiviral research · 2025Article
- HSF1 Activation Mechanisms, Disease Roles, and Small Molecule Therapeutics.International journal of biological sciences · 2025Review
- Review
- Article
- ER Stress-Activated HSF1 Governs Cancer Cell Resistance to USP7 Inhibitor-Based Chemotherapy through the PERK Pathway.International journal of molecular sciences · 2024Article
- Disrupted HSF1 regulation in normal and exceptional brain aging.Biogerontology · 2024Article
- Mitochondrial p38 Mitogen-Activated Protein Kinase: Insights into Its Regulation of and Role in LONP1-Deficient Nematodes.International journal of molecular sciences · 2023Article
- Review
- Pathways to healing: Plants with therapeutic potential for neurodegenerative diseases.IBRO neuroscience reports · 2023Article
- Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP Suppression.Biomedicines · 2023Article
- Targeting HSF1 for cancer treatment: mechanisms and inhibitor development.Theranostics · 2023Review
- Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer's disease.Natural products and bioprospecting · 2022Article
- AKT1 mediates multiple phosphorylation events that functionally promote HSF1 activation.The FEBS journal · 2022Article
- Heat Shock Proteins and HSF1 in Cancer.Frontiers in oncology · 2022Review
- Heat shock factor 1 suppression induces spindle abnormalities and sensitizes cells to antimitotic drugs.Cell division · 2021Article
- Article
- The stress-responsive kinase DYRK2 activates heat shock factor 1 promoting resistance to proteotoxic stress.Cell death and differentiation · 2021Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
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.
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Registered trials
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.