ArticleThe EMBO journal2012
Metazoan Hsp70 machines use Hsp110 to power protein disaggregation.
Article in The EMBO journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
189 citing papers in PubMed, 319 citations in OpenAlex.
- From aggregate structure to disease trajectory: the role of the proteostasis network.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Hsp70 diversification and repurposing across the tree of life: Lessons from the evolutionary and mechanistic trajectory of the Hsp70-Hsp110 chaperone system.The FEBS journal · 2026Review
- Mixed-class J-domain protein scaffolds promote expanded aggregate handling and multivalent Hsp70 engagement during functional disaggregase assembly.FEBS letters · 2026Article
- ATP modulates holdase activity of fungal and human 110-kilodalton heat shock proteins to promote protein folding.Protein science : a publication of the Protein Society · 2026Article
- DNAJB4 Protects Against Atherosclerosis by Stabilizing the HSP70-LXRα Axis in Hepatic Lipid Metabolism.International journal of biological sciences · 2026Article
- Contrasting roles of autophagy in cellular prion infection.Autophagy · 2025Article
- Structural polymorphism of α-synuclein fibrils alters the pathway of Hsc70-mediated disaggregation.The EMBO journal · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Competing chaperone pathways in α-synuclein disaggregation and aggregation dynamics.Protein science : a publication of the Protein Society · 2025Article
- How does protein aggregate structure affect mechanisms of disaggregation?Biochemical Society transactions · 2025Review
- Biochemical and biophysical characterization of Plasmodium falciparum glucose regulated protein 170.Scientific reports · 2025Article
- Review
- HSP110 is a modulator of amyloid beta (Aβ) aggregation and proteotoxicity.Journal of neurochemistry · 2025Article
- Characterization of a New Hsp110 Inhibitor as a Potential Antifungal.Journal of fungi (Basel, Switzerland) · 2024Article
- Early steps of protein disaggregation by Hsp70 chaperone and class B J-domain proteins are shaped by Hsp110.eLife · 2024Article
- The middle domain of Hsp104 can ensure substrates are functional after processing.PLoS genetics · 2024Article
- The Essential Functions of Molecular Chaperones and Folding Enzymes in Maintaining Endoplasmic Reticulum Homeostasis.Journal of molecular biology · 2024Review
- Review
- Protein aggregation and biomolecular condensation in hypoxic environments (Review).International journal of molecular medicine · 2024Review
- Sequestrase chaperones protect against oxidative stress-induced protein aggregation and [PSI+] prion formation.PLoS genetics · 2024Article
129 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Accumulation of aggregation-prone misfolded proteins disrupts normal cellular function and promotes ageing and disease. Bacteria, fungi and plants counteract this by solubilizing and refolding aggregated proteins via a powerful cytosolic ATP-dependent bichaperone system, comprising the AAA+ disaggregase Hsp100 and the Hsp70-Hsp40 system. Metazoa, however, lack Hsp100 disaggregases. We show that instead the Hsp110 member of the Hsp70 superfamily remodels the human Hsp70-Hsp40 system to efficiently disaggregate and refold aggregates of heat and chemically denatured proteins in vitro and in cell extracts. This Hsp110 effect relies on nucleotide exchange, not on ATPase activity, implying ATP-driven chaperoning is not required. Knock-down of nematode Caenorhabditis elegans Hsp110, but not an unrelated nucleotide exchange factor, compromises dissolution of heat-induced protein aggregates and severely shortens lifespan after heat shock. We conclude that in metazoa, Hsp70-Hsp40 powered by Hsp110 nucleotide exchange represents the crucial disaggregation machinery that reestablishes protein homeostasis to counteract protein unfolding stress.
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What OpenQuestion holds
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.