ArticlePloS one2012
mTOR is essential for the proteotoxic stress response, HSF1 activation and heat shock protein synthesis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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The trial behind it
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Who cites it
125 citing papers in PubMed, 231 citations in OpenAlex.
- Trial
- Article
- 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
- Repeated Moderate and Severe Heat Exposure Has Divergent Effects on Skeletal Muscle Mitochondrial, Proteostatic and Neuromuscular Outcomes in Mice.Acta physiologica (Oxford, England) · 2026Article
- A Function-Centric Framework for Mitochondrial Quality Control.Biomolecules · 2026Review
- Chronic Lithium Exposure Reshapes PI3K-mTOR-linked Proteostatic Networks in the Hippocampus of an Alzheimer's Disease Mouse Model.Molecular neurobiology · 2026Article
- Spatially resolved ex vivo drug response profiling in SMARCB1-deficient sinonasal carcinoma.EMBO molecular medicine · 2026Article
- mTOR signaling regulates demand-adapted hematopoiesis and metabolic reprogramming required for an effective cellular immune response in Drosophila melanogaster larvae.PLoS genetics · 2026Article
- Ribosome biogenesis as a potential therapeutic target in KRAS mutant colorectal cancer.Nature communications · 2025Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Targeting the host transcription factor HSF1 prevents human cytomegalovirus replication in vitro and in vivo.Antiviral research · 2025Article
- Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune aging.Frontiers in immunology · 2025Review
- Review
- Bag-1-mediated HSF1 phosphorylation regulates expression of heat shock proteins in breast cancer cells.FEBS open bio · 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
- Ac-HSP20 regulates autophagy and promotes the encystation of Acanthamoeba castellanii by inhibiting the PI3K/AKT/mTOR signaling pathway.Parasites & vectors · 2024Article
- Interplay between mTOR and Purine Metabolism Enzymes and Its Relevant Role in Cancer.International journal of molecular sciences · 2024Review
- ER Stress-Activated HSF1 Governs Cancer Cell Resistance to USP7 Inhibitor-Based Chemotherapy through the PERK Pathway.International journal of molecular sciences · 2024Article
- HSF1 at the crossroads of chemoresistance: from current insights to future horizons in cell death mechanisms.Frontiers in cell and developmental biology · 2024Review
- Heat Shock Factor 1 Inhibition: A Novel Anti-Cancer Strategy with Promise for Precision Oncology.Cancers · 2023Review
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The target of rapamycin (TOR) is a high molecular weight protein kinase that regulates many processes in cells in response to mitogens and variations in nutrient availability. Here we have shown that mTOR in human tissue culture cells plays a key role in responses to proteotoxic stress and that reduction in mTOR levels by RNA interference leads to increase sensitivity to heat shock. This effect was accompanied by a drastic reduction in ability to synthesize heat shock proteins (HSP), including Hsp70, Hsp90 and Hsp110. As HSP transcription is regulated by heat shock transcription factor 1 (HSF1), we examined whether mTOR could directly phosphorylate this factor. Indeed, we determined that mTOR could directly phosphorylate HSF1 on serine 326, a key residue in transcriptional activation. HSF1 was phosphorylated on S326 immediately after heat shock and was triggered by other cell stressors including proteasome inhibitors and sodium arsenite. Null mutation of S326 to alanine led to loss of ability to activate an HSF1-regulated promoter-reporter construct, indicating a direct role for mTOR and S326 in transcriptional regulation of HSP genes during stress. As mTOR is known to exist in at least two intracellular complexes, mTORC1 and mTOR2 we examined which complex might interact with HSF1. Indeed mTORC1 inhibitor rapamycin prevented HSF1-S326 phosphorylation, suggesting that this complex is involved in HSF1 regulation in stress. Our experiments therefore suggest a key role for mTORC1 in transcriptional responses to proteotoxic stress.
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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.