ArticleMolecular and cellular biology2003
Regulation of molecular chaperone gene transcription involves the serine phosphorylation, 14-3-3 epsilon binding, and cytoplasmic sequestration of heat shock factor 1.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 120 citations in OpenAlex.
- A discovery-based proteomic approach of epidermal growth factor and growth hormone-releasing peptide-6 in a model of acute ischemic stroke.Pharmacological reports : PR · 2026Article
- Liver-specific SIRT1 knockout-induced hyperglycemia promotes spontaneous lung adenocarcinomas through HSF1-MDM2.Oncogene · 2026Article
- Real-time visualization of reconstituted transcription reveals RNAPII activation mechanisms at single promoters.Cell reports · 2025Article
- Real-time visualization of reconstituted transcription reveals RNA polymerase II activation mechanisms at single promoters.bioRxiv : the preprint server for biology · 2025Article
- Discovery of Disubstituted Carboranes as Inhibitors of Heat Shock Protein 90-Heat Shock Factor 1 Interaction.ACS medicinal chemistry letters · 2024Article
- ER Stress-Activated HSF1 Governs Cancer Cell Resistance to USP7 Inhibitor-Based Chemotherapy through the PERK Pathway.International journal of molecular sciences · 2024Article
- Stress biology: Complexity and multifariousness in health and disease.Cell stress & chaperones · 2024Article
- Human herpesvirus 6A nuclear matrix protein U37 interacts with heat shock transcription factor 1 and activates the heat shock response.Journal of virology · 2023Article
- Targeted Replacement of HSF1 Phosphorylation Sites at S303/S307 with Alanine Residues in Mice Increases Cell Proliferation and Drug Resistance.Methods in molecular biology (Clifton, N.J.) · 2023Article
- AKT1 mediates multiple phosphorylation events that functionally promote HSF1 activation.The FEBS journal · 2022Article
- Domesticated LTR-RetrotransposonLife (Basel, Switzerland) · 2022Review
- HSF-1: Guardian of the Proteome Through Integration of Longevity Signals to the Proteostatic Network.Frontiers in aging · 2022Review
- Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress.Cells · 2021Article
- The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response.Archives of toxicology · 2021Review
- The proteostasis guardian HSF1 directs the transcription of its paralog and interactor HSF2 during proteasome dysfunction.Cellular and molecular life sciences : CMLS · 2021Article
- Understanding and exploiting interactions between cellular proteostasis pathways and infectious prion proteins for therapeutic benefit.Open biology · 2020Article
- RNA aptamer capture of macromolecular complexes for mass spectrometry analysis.Nucleic acids research · 2020Article
- Harnessing the Proteostasis Network in Alcohol-associated Liver Disease.Current pathobiology reports · 2020Article
- Decreased expression of FBXW7 by ERK1/2 activation in drug-resistant cancer cells confers transcriptional activation of MDR1 by suppression of ubiquitin degradation of HSF1.Cell death & disease · 2020Article
- Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1.Experimental & molecular medicine · 2020Article
1 more citing papers are in PubMed but not listed here.
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4 authors at 2 institutions in 1 country.
Funding
Abstract
Heat shock factor 1 (HSF1) regulates the transcription of molecular chaperone hsp genes. However, the cellular control mechanisms that regulate HSF1 activity are not well understood. In this study, we have demonstrated for the first time that human HSF1 binds to the essential cell signaling protein 14-3-3 epsilon. Binding of HSF1 to 14-3-3 epsilon occurs in cells in which extracellular signal regulated kinase (ERK) is activated and blockade of the ERK pathway by treatment with the specific ERK pathway inhibitor PD98059 in vivo strongly suppresses the binding. We previously showed that ERK1 phosphorylates HSF1 on serine 307 and leads to secondary phosphorylation by glycogen synthase kinase 3 (GSK3) on serine 303 within the regulatory domain and that these phosphorylation events repress HSF1. We show here that HSF1 binding to 14-3-3 epsilon requires HSF1 phosphorylation on serines 303 and 307. Furthermore, the serine phosphorylation-dependent binding of HSF1 to 14-3-3 epsilon results in the transcriptional repression of HSF1 and its sequestration in the cytoplasm. Leptomycin B, a specific inhibitor of nuclear export receptor CRM1, was found to reverse the cytoplasmic sequestration of HSF1 mediated by 14-3-3 epsilon, suggesting that CRM1/14-3-3 epsilon directed nuclear export plays a major role in repression of HSF1 by the ERK/GSK3/14-3-3 epsilon pathway. Our experiments indicate a novel pathway for HSF1 regulation and suggest a mechanism for suppression of its activity during cellular proliferation.
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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.