ArticleCell stress & chaperones2012
Heat shock factor 1 is inactivated by amino acid deprivation.
Article in Cell stress & chaperones, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Proteomic and phenotypic profiling of replicative-senescent human foreskin fibroblasts under brief heat shock.Cell stress & chaperones · 2026Article
- ER Stress-Related Biomarkers in Chronic Obstructive Pulmonary Disease: A Comprehensive Transcriptome, Mendelian Randomization, and Machine-Learning Analysis.International journal of chronic obstructive pulmonary disease · 2025Article
- Transcriptomic and Proteomic Insights into Host Immune Responses in Pediatric Severe Malarial Anemia: Dysregulation in HSP60-70-TLR2/4 Signaling and Altered Glutamine Metabolism.Pathogens (Basel, Switzerland) · 2024Article
- Resolution of inflammation in chronic disease via restoration of the heat shock response (HSR).Cell stress & chaperones · 2024Review
- Article
- HSF1 Pathway Inhibitor Clinical Candidate (CCT361814/NXP800) Developed from a Phenotypic Screen as a Potential Treatment for Refractory Ovarian Cancer and Other Malignancies.Journal of medicinal chemistry · 2023Article
- c-MYC-mediated TRIB3/P62Acta pharmaceutica Sinica. B · 2022Article
- Article
- Amino acid restriction alters survival mechanisms in pancreatic beta cells: possible role of the PI3K/Akt pathway.European journal of nutrition · 2021Article
- Identification of key Genes and Pathways Associated With Thermal Stress in Peripheral Blood Mononuclear Cells of Holstein Dairy Cattle.Frontiers in genetics · 2021Article
- Cell-Nonautonomous Regulation of Proteostasis in Aging and Disease.Cold Spring Harbor perspectives in biology · 2020Review
- Wnt regulates amino acid transporter Slc7a5 and so constrains the integrated stress response in mouse embryos.EMBO reports · 2020Article
- Cellular stress mechanisms of prenatal maternal stress: Heat shock factors and oxidative stress.Neuroscience letters · 2019Review
- Gene networking in colistin-induced nephrotoxicity reveals an adverse outcome pathway triggered by proteotoxic stress.International journal of molecular medicine · 2019Article
- Dietary Nutrients and Bioactive Substances Modulate Heat Shock Protein (HSP) Expression: A Review.Nutrients · 2018Review
- Article
- Rethinking HSF1 in Stress, Development, and Organismal Health.Trends in cell biology · 2017Review
- Metabolic control of the proteotoxic stress response: implications in diabetes mellitus and neurodegenerative disorders.Cellular and molecular life sciences : CMLS · 2016Review
- Cloning and Transcriptional Activity of the Mouse Omi/HtrA2 Gene Promoter.International journal of molecular sciences · 2016Article
- Suppression of the HSF1-mediated proteotoxic stress response by the metabolic stress sensor AMPK.The EMBO journal · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian cells respond to a lack of amino acids by activating a transcriptional program with the transcription factor ATF4 as one of the main actors. When cells are faced with cytoplasmic proteotoxic stress, a quite different transcriptional response is mounted, the heat shock response, which is mediated by HSF1. Here, we show that amino acid deprivation results in the inactivation of HSF1. In amino acid deprived cells, active HSF1 loses its DNA binding activity as demonstrated by EMSA and ChIP. A sharp decrease in the transcript level of HSF1 target genes such as HSPA1A (Hsp70), DNAJB1 (Hsp40), and HSP90AA1 is also seen. HSPA1A mRNA, but not DNAJB1 mRNA, was also destabilized. In cells cultured with limiting leucine, HSF1 activity also declined. Lack of amino acids thus could lead to a lower chaperoning capacity and cellular frailty. We show that the nutrient sensing response unit of the ASNS gene contains an HSF1 binding site, but we could not detect binding of HSF1 to this site in vivo. Expression of either an HSF1 mutant lacking the activation domain (HSF379) or an HSF1 mutant unable to bind DNA (K80Q) had only a minor effect on the transcript levels of amino acid deprivation responsive genes.
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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.