ArticleNature chemical biology2013
ATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system.
Article in Nature chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 147 citations in OpenAlex.
- Rapid activation of ARF6 after RAF inhibition augments BRAFOncogene · 2026Article
- Development of a chaperone-mediated protein degrader targeting ERK5 that efficaciously reduces tumor growth.Cell communication and signaling : CCS · 2026Article
- Article
- Design of multi-target peptide modulators for protein chaperone networks.Structure (London, England : 1993) · 2025Article
- Mechanisms that matter: unbiased cellular screening for degraders.npj drug discovery · 2025Review
- Rapid activation of ARF6 after RAF inhibition augments BRAFV600E and promotes therapy resistance.Research square · 2025Article
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- A fluorescence-based sensor for calibrated measurement of protein kinase stability in live cells.Protein science : a publication of the Protein Society · 2024Article
- Predictive value of CDC37 gene expression for targeted therapy in metastatic colorectal cancer.European journal of cancer (Oxford, England : 1990) · 2024Article
- Structural dynamics of RAF1-HSP90-CDC37 and HSP90 complexes reveal asymmetric client interactions and key structural elements.Communications biology · 2024Article
- PIM1 targeted degradation prevents the emergence of chemoresistance in prostate cancer.Cell chemical biology · 2024Article
- Induced protein degradation for therapeutics: past, present, and future.The Journal of clinical investigation · 2024Review
- ZIKV prM hijacks PIM1 kinase for phosphorylation to prevent ubiquitin-mediated degradation and facilitate viral replication.Frontiers in cellular and infection microbiology · 2024Article
- A Fluorescence-Based Sensor for Calibrated Measurement of Protein Kinase Stability in Live Cells.bioRxiv : the preprint server for biology · 2023Article
- Saccharomyces cerevisiae as a tool for deciphering Hsp90 molecular chaperone function.Essays in biochemistry · 2023Article
- Catalytic Degraders Effectively Address Kinase Site Mutations in EML4-ALK Oncogenic Fusions.Journal of medicinal chemistry · 2023Article
- Hsp90 provides a platform for kinase dephosphorylation by PP5.Nature communications · 2023Article
- The importance of controls in targeted protein degradation: Determining mechanism.Methods in enzymology · 2023Article
- HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation.Nature communications · 2022Article
- Discovery of a tetrahydroisoquinoline-based CDK9-cyclin T1 protein-protein interaction inhibitor as an anti-proliferative and anti-migration agent against triple-negative breast cancer cells.Genes & diseases · 2022Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Protein kinase clients are recruited to the Hsp90 molecular chaperone system via Cdc37, which simultaneously binds Hsp90 and kinases and regulates the Hsp90 chaperone cycle. Pharmacological inhibition of Hsp90 in vivo results in degradation of kinase clients, with a therapeutic effect in dependent tumors. We show here that Cdc37 directly antagonizes ATP binding to client kinases, suggesting a role for the Hsp90-Cdc37 complex in controlling kinase activity. Unexpectedly, we find that Cdc37 binding to protein kinases is itself antagonized by ATP-competitive kinase inhibitors, including vemurafenib and lapatinib. In cancer cells, these inhibitors deprive oncogenic kinases such as B-Raf and ErbB2 of access to the Hsp90-Cdc37 complex, leading to their degradation. Our results suggest that at least part of the efficacy of ATP-competitive inhibitors of Hsp90-dependent kinases in tumor cells may be due to targeted chaperone deprivation.
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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.