ArticlePloS one2015
Client Proteins and Small Molecule Inhibitors Display Distinct Binding Preferences for Constitutive and Stress-Induced HSP90 Isoforms and Their Conformationally Restricted Mutants.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
42 citing papers in PubMed, 58 citations in OpenAlex.
- Targeting the 4EBP1/HSP90β/Nrf2 Axis Sensitizes β-catenin-mutant Hepatocellular Carcinoma to mTOR Inhibitors via Ferroptosis Induction.Journal of clinical and translational hepatology · 2026Article
- FKBP8 connects the Hsp70-Hsp90 chaperone machinery to the folding of membrane proteins.Nature communications · 2026Article
- Functional interplay between heat shock protein 90 (HSP90) and heat shock factors (HSFs).Cell stress & chaperones · 2026Review
- HSP90B1 facilitates glioma radiotherapy resistance by regulating RhoC ubiquitin‒proteasome degradation.Genes & diseases · 2026Article
- Embracing diversity: Post-translational modifications, the chaperone code, and the emergence of new chaperone entities.Cell stress & chaperones · 2026Review
- Nrf2-Keap1 Pathway and NLRP3 Inflammasome in Parkinson's Disease: Mechanistic Crosstalk and Therapeutic Implications.Molecular neurobiology · 2025Review
- Elevated plasma HSP90α as a prognostic marker in EGFR-mutant non-small cell lung cancer.Oncology letters · 2025Article
- The Hsp90β Isoform: An Attractive Target for Drug Development.Medicinal research reviews · 2025Review
- Assessment of Hsp90β-selective inhibitor safety and on-target effects.Scientific reports · 2025Article
- Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases.Genes and immunity · 2024Review
- A fluorescence-based sensor for calibrated measurement of protein kinase stability in live cells.Protein science : a publication of the Protein Society · 2024Article
- A Fluorescence-Based Sensor for Calibrated Measurement of Protein Kinase Stability in Live Cells.bioRxiv : the preprint server for biology · 2023Article
- Extracellular Hsp90 Binds to and Aligns Collagen-1 to Enhance Breast Cancer Cell Invasiveness.Cancers · 2023Article
- The Role of the Transcription Factor Nrf2 in Alzheimer's Disease: Therapeutic Opportunities.Biomolecules · 2023Review
- The Mitochondrial HSP90 Paralog TRAP1: Structural Dynamics, Interactome, Role in Metabolic Regulation, and Inhibitors.Biomolecules · 2022Review
- A novel yeast model detects Nrf2 and Keap1 interactions with Hsp90.Disease models & mechanisms · 2022Article
- Heat increases full-length SMN splicing: promise for splice-augmenting therapies for SMA.Human genetics · 2022Article
- HSP70 and HSP90 in Cancer: Cytosolic, Endoplasmic Reticulum and Mitochondrial Chaperones of Tumorigenesis.Frontiers in oncology · 2022Review
- Structure-Based Design, Synthesis, and Biological Evaluation of Hsp90β-Selective Inhibitors.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The two cytosolic/nuclear isoforms of the molecular chaperone HSP90, stress-inducible HSP90α and constitutively expressed HSP90β, fold, assemble and maintain the three-dimensional structure of numerous client proteins. Because many HSP90 clients are important in cancer, several HSP90 inhibitors have been evaluated in the clinic. However, little is known concerning possible unique isoform or conformational preferences of either individual HSP90 clients or inhibitors. In this report, we compare the relative interaction strength of both HSP90α and HSP90β with the transcription factors HSF1 and HIF1α, the kinases ERBB2 and MET, the E3-ubiquitin ligases KEAP1 and RHOBTB2, and the HSP90 inhibitors geldanamycin and ganetespib. We observed unexpected differences in relative client and drug preferences for the two HSP90 isoforms, with HSP90α binding each client protein with greater apparent affinity compared to HSP90β, while HSP90β bound each inhibitor with greater relative interaction strength compared to HSP90α. Stable HSP90 interaction was associated with reduced client activity. Using a defined set of HSP90 conformational mutants, we found that some clients interact strongly with a single, ATP-stabilized HSP90 conformation, only transiently populated during the dynamic HSP90 chaperone cycle, while other clients interact equally with multiple HSP90 conformations. These data suggest different functional requirements among HSP90 clientele that, for some clients, are likely to be ATP-independent. Lastly, the two inhibitors examined, although sharing the same binding site, were differentially able to access distinct HSP90 conformational states.
Indexed as
Identifiers
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.