ArticleCell reports2015
c-Abl Mediated Tyrosine Phosphorylation of Aha1 Activates Its Co-chaperone Function in Cancer Cells.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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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.
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Who cites it
49 citing papers in PubMed, 70 citations in OpenAlex.
- AHSA1 promotes the progression of lung cancer by enhancing the expression of HSP90α.Histology and histopathology · 2026Article
- Optimization of Hsp90/Aha1 Small-Molecule Disruptors Via the Evaluation of Amide Bioisosteres.ACS medicinal chemistry letters · 2025Article
- Ex vivo qualitative and quantitative analysis of fluorescently-labeled Hsp90 drug in human tumors.Cell stress & chaperones · 2025Article
- Collaboration between two conserved sequence motifs drives ATPase stimulation of Hsp90 by Aha1.Protein science : a publication of the Protein Society · 2025Article
- Article
- Ordered ATP hydrolysis in the Hsp90 chaperone is regulated by Aha1 and a conserved post-translational modification.Protein science : a publication of the Protein Society · 2025Article
- Review
- The role of Aha1 in cancer and neurodegeneration.Frontiers in molecular neuroscience · 2024Review
- Structural and functional complexity of HSP90 in cellular homeostasis and disease.Nature reviews. Molecular cell biology · 2023Review
- Saccharomyces cerevisiae as a tool for deciphering Hsp90 molecular chaperone function.Essays in biochemistry · 2023Article
- Epichaperomics reveals dysfunctional chaperone protein networks.Nature communications · 2023Article
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular Carcinoma.Cancers · 2022Article
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- Synthesis and Evaluation of Small Molecule Disruptors of the Aha1/Hsp90 Complex for the Reduction of Tau Aggregation.ACS medicinal chemistry letters · 2022Article
- Inhibitors of theCells · 2021Review
- AHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas.Scientific reports · 2021Article
- Aha1 Exhibits Distinctive Dynamics Behavior and Chaperone-Like Activity.Molecules (Basel, Switzerland) · 2021Article
- The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma.Molecular cell · 2021Article
- Hsp90 modulates human sperm capacitation via the Erk1/2 and p38 MAPK signaling pathways.Reproductive biology and endocrinology : RB&E · 2021Article
Corrections and comments
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Authors and funding
25 authors at 12 institutions in 3 countries.
Funding
Abstract
The ability of Heat Shock Protein 90 (Hsp90) to hydrolyze ATP is essential for its chaperone function. The co-chaperone Aha1 stimulates Hsp90 ATPase activity, tailoring the chaperone function to specific "client" proteins. The intracellular signaling mechanisms directly regulating Aha1 association with Hsp90 remain unknown. Here, we show that c-Abl kinase phosphorylates Y223 in human Aha1 (hAha1), promoting its interaction with Hsp90. This, consequently, results in an increased Hsp90 ATPase activity, enhances Hsp90 interaction with kinase clients, and compromises the chaperoning of non-kinase clients such as glucocorticoid receptor and CFTR. Suggesting a regulatory paradigm, we also find that Y223 phosphorylation leads to ubiquitination and degradation of hAha1 in the proteasome. Finally, pharmacologic inhibition of c-Abl prevents hAha1 interaction with Hsp90, thereby hypersensitizing cancer cells to Hsp90 inhibitors both in vitro and ex vivo.
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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.