ArticleACS chemical biology2010
Binding of a small molecule at a protein-protein interface regulates the chaperone activity of hsp70-hsp40.
Article in ACS chemical biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 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.
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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
97 citing papers in PubMed, 161 citations in OpenAlex.
- Wiring of cellular proteostasis by J-domain proteins.Cell stress & chaperones · 2026Review
- Inhibition of the assembly ofmBio · 2025Article
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- Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease.Cells · 2025Review
- Assays to measure small molecule Hsp70 agonist activity in vitro and in vivo.Analytical biochemistry · 2025Article
- Co-chaperones fine-tune the function of heat shock protein 70 (Hsp70), whether to fold, hold, or degrade substrates in ensuring cellular protein homeostasis.Journal of biosciences · 2025Review
- J-domain proteins: From molecular mechanisms to diseases.Cell stress & chaperones · 2024Article
- Non-Essential Amino Acid Availability Influences Proteostasis and Breast Cancer Cell Survival During Proteotoxic Stress.Molecular cancer research : MCR · 2023Article
- The MitoLuc Assay System for Accurate Real-Time Monitoring of Mitochondrial Protein Import Within Mammalian Cells.Journal of molecular biology · 2023Article
- Synthetic Small Molecule Modulators of Hsp70 and Hsp40 Chaperones as Promising Anticancer Agents.International journal of molecular sciences · 2023Review
- J-domain protein chaperone circuits in proteostasis and disease.Trends in cell biology · 2023Review
- Article
- TheFrontiers in molecular biosciences · 2023Review
- Identification of new small molecules as dual FoxM1 and Hsp70 inhibitors using computational methods.Research in pharmaceutical sciences · 2022Article
- Multivalent protein-protein interactions are pivotal regulators of eukaryotic Hsp70 complexes.Cell stress & chaperones · 2022Review
- The APE2 Exonuclease Is a Client of the Hsp70-Hsp90 Axis in Yeast and Mammalian Cells.Biomolecules · 2022Article
- Non-Equilibrium Protein Folding and Activation by ATP-Driven Chaperones.Biomolecules · 2022Article
- The HSP40 chaperone Ydj1 drives amyloid beta 42 toxicity.EMBO molecular medicine · 2022Article
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
37 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
13 authors at 2 institutions in 1 country.
Funding
Abstract
Heat shock protein 70 (Hsp70) is a highly conserved molecular chaperone that plays multiple roles in protein homeostasis. In these various tasks, the activity of Hsp70 is shaped by interactions with co-chaperones, such as Hsp40. The Hsp40 family of co-chaperones binds to Hsp70 through a conserved J-domain, and these factors stimulate ATPase and protein-folding activity. Using chemical screens, we identified a compound, 115-7c, which acts as an artificial co-chaperone for Hsp70. Specifically, the activities of 115-7c mirrored those of a Hsp40; the compound stimulated the ATPase and protein-folding activities of a prokaryotic Hsp70 (DnaK) and partially compensated for a Hsp40 loss-of-function mutation in yeast. Consistent with these observations, NMR and mutagenesis studies indicate that the binding site for 115-7c is adjacent to a region on DnaK that is required for J-domain-mediated stimulation. Interestingly, we found that 115-7c and the Hsp40 do not compete for binding but act in concert. Using this information, we introduced additional steric bulk to 115-7c and converted it into an inhibitor. Thus, these chemical probes either promote or inhibit chaperone functions by regulating Hsp70-Hsp40 complex assembly at a native protein-protein interface. This unexpected mechanism may provide new avenues for exploring how chaperones and co-chaperones cooperate to shape protein homeostasis.
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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.