ArticleCell reports2019
Co-chaperones TIMP2 and AHA1 Competitively Regulate Extracellular HSP90:Client MMP2 Activity and Matrix Proteolysis.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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.
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Who cites it
52 citing papers in PubMed, 75 citations in OpenAlex.
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- Autophagy Orchestrates Anti-Tumor Immunity to Enhance Chemosensitivity via the FBXW2/C/EBPβ/TIMP-2 Axis in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Development of a chaperone-mediated protein degrader targeting ERK5 that efficaciously reduces tumor growth.Cell communication and signaling : CCS · 2026Article
- Unconventional Secretion of Angiogenic Sonic Hedgehog-Containing Extra-Large Extracellular Vesicles is Driven by PI3K-Rab18-GDP Signalling.Journal of extracellular biology · 2026Article
- Article
- Targeting and dissociating HIF2α from the molecular chaperone Hsp70 triggers apoptosis in kidney cancer.Communications medicine · 2026Article
- HSP90α and KLK6 Co-Regulate Stress-Induced Prostate Cancer Cell Motility.bioRxiv : the preprint server for biology · 2025Article
- Review
- TGF-β2 increases eHSP90α secretion via upregulating secretory autophagy pathway.Cell communication and signaling : CCS · 2025Article
- Benzbromarone interferes with the interaction between Hsp90 and Aha1 by interacting with both of them.Communications biology · 2025Article
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Hsp90: Bringing it all together.Cell stress & chaperones · 2025Review
- Diamond Nanoparticles Suppress Migration of T98G Glioblastoma Cells by Targeting ECM-Integrin Interactions and Intracellular Signaling, Leading to Extensive Proteome Alterations.Nanotechnology, science and applications · 2025Article
- The Role of eHsp90 in Extracellular Matrix Remodeling, Tumor Invasiveness, and Metastasis.Cancers · 2024Review
- The Downregulation of MMP23B Facilitates the Suppression of Vitality and Induction of Apoptosis in Endometrial Cancer Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Mapping Extracellular Protein-Protein Interactions Using Extracellular Proximity Labeling (ePL).Journal of proteome research · 2024Article
- Review
- Extracellular Proximity Labeling Reveals an Expanded Interactome for the Matrisome Protein TIMP2.Research square · 2024Article
- The role of Aha1 in cancer and neurodegeneration.Frontiers in molecular neuroscience · 2024Review
- Tissue inhibitors of metalloproteinases are proteolytic targets of matrix metalloproteinase 9.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
The extracellular molecular chaperone heat shock protein 90 (eHSP90) stabilizes protease client the matrix metalloproteinase 2 (MMP2), leading to tumor cell invasion. Although co-chaperones are critical modulators of intracellular HSP90:client function, how the eHSP90:MMP2 complex is regulated remains speculative. Here, we report that the tissue inhibitor of metalloproteinases-2 (TIMP2) is a stress-inducible extracellular co-chaperone that binds to eHSP90, increases eHSP90 binding to ATP, and inhibits its ATPase activity. In addition to disrupting the eHSP90:MMP2 complex and terminally inactivating MMP2, TIMP2 loads the client to eHSP90, keeping the protease in a transient inhibitory state. Secreted activating co-chaperone AHA1 displaces TIMP2 from the complex, providing a "reactivating" mechanism for MMP2. Gene knockout or blocking antibodies targeting TIMP2 and AHA1 released by HT1080 cancer cells modify their gelatinolytic activity. Our data suggest that TIMP2 and AHA1 co-chaperones function as a molecular switch that determines the inhibition and reactivation of the eHSP90 client protein MMP2.
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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.