ArticleThe EMBO journal2015
Suppression of the HSF1-mediated proteotoxic stress response by the metabolic stress sensor AMPK.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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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
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Targeting cellular senescence with Traditional Chinese Medicine: advances in neurodegenerative disorder treatment.Frontiers in neurology · 2026Pooled it
- Effects of Alanyl-Glutamine Treatment on the Peritoneal Dialysis Effluent Proteome Reveal Pathomechanism-Associated Molecular Signatures.Molecular & cellular proteomics : MCP · 2018Trial
- Adaptation to heat stress by diversification of the vertebrate heat shock transcription factor family.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
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- Cancer suppresses mitochondrial chaperone activity in macrophages to drive immune evasion.Nature immunology · 2025Article
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- BAP1 regulates HSF1 activity and cancer immunity in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Hsp70 Negatively Regulates Autophagy via Governing AMPK Activation, and Dual Hsp70-Autophagy Inhibition Induces Synergetic Cell Death in NSCLC Cells.International journal of molecular sciences · 2024Article
- Resolution of inflammation in chronic disease via restoration of the heat shock response (HSR).Cell stress & chaperones · 2024Review
- Heat shock response during the resolution of inflammation and its progressive suppression in chronic-degenerative inflammatory diseases.Cell stress & chaperones · 2024Review
- The dance of proteostasis and metabolism: Unveiling the caloristatic controlling switch.Cell stress & chaperones · 2024Review
- Article
- HSF1 at the crossroads of chemoresistance: from current insights to future horizons in cell death mechanisms.Frontiers in cell and developmental biology · 2024Review
- Increased mitochondria are responsible for the acquisition of gemcitabine resistance in pancreatic cancer cell lines.Cancer science · 2023Article
- Heat shock factor 1 (HSF1) specifically potentiates c-MYC-mediated transcription independently of the canonical heat shock response.Cell reports · 2023Article
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Targeting HSF1 for cancer treatment: mechanisms and inhibitor development.Theranostics · 2023Review
- Proteotoxic stress response in atherosclerotic cardiovascular disease: Emerging role of heat shock factor 1.Frontiers in cardiovascular medicine · 2023Review
- The RNA polymerase of cytoplasmically replicating Zika virus binds with chromatin DNA in nuclei and regulates host gene transcription.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Transcriptomics-based network medicine approach identifies metformin as a repurposable drug for atrial fibrillation.Cell reports. Medicine · 2022Article
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7 authors at 1 institution in 1 country.
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Abstract
Numerous extrinsic and intrinsic insults trigger the HSF1-mediated proteotoxic stress response (PSR), an ancient transcriptional program that is essential to proteostasis and survival under such conditions. In contrast to its well-recognized mobilization by proteotoxic stress, little is known about how this powerful adaptive mechanism reacts to other stresses. Surprisingly, we discovered that metabolic stress suppresses the PSR. This suppression is largely mediated through the central metabolic sensor AMPK, which physically interacts with and phosphorylates HSF1 at Ser121. Through AMPK activation, metabolic stress represses HSF1, rendering cells vulnerable to proteotoxic stress. Conversely, proteotoxic stress inactivates AMPK and thereby interferes with the metabolic stress response. Importantly, metformin, a metabolic stressor and popular anti-diabetic drug, inactivates HSF1 and provokes proteotoxic stress within tumor cells, thereby impeding tumor growth. Thus, these findings uncover a novel interplay between the metabolic stress sensor AMPK and the proteotoxic stress sensor HSF1 that profoundly impacts stress resistance, proteostasis, and malignant growth.
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