ArticleProceedings of the National Academy of Sciences of the United States of America2016
Structural and functional basis of protein phosphatase 5 substrate specificity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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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
47 citing papers in PubMed, 85 citations in OpenAlex.
- Shifting paradigms: phosphatases from basic biology to druggable targets.Biology open · 2026Article
- PPM1B utilizes a trinuclear metal architecture for phosphatase activity.bioRxiv : the preprint server for biology · 2026Article
- De-repression of protein phosphatase 5 by the chaperone organizer HOP1 activates plant NLR immunity.Nature plants · 2026Article
- Structural bases of signal generation and transduction by the SPS amino acid sensor of Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2026Article
- GSK3β-driven phosphorylation of ABLIM1 regulates its interactions with titin cardiac muscle.The Journal of general physiology · 2025Article
- The known unknowns of the Hsp90 chaperone.eLife · 2024Review
- SUMOylation of protein phosphatase 5 regulates phosphatase activity and substrate release.EMBO reports · 2024Article
- Reversible control of kinase signaling through chemical-induced dephosphorylation.Communications biology · 2024Article
- Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90.Nature communications · 2024Article
- Small molecules targeting protein-protein interactions for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Activation of autophagy depends on Atg1/Ulk1-mediated phosphorylation and inhibition of the Hsp90 chaperone machinery.Cell reports · 2023Article
- Hsp90 provides a platform for kinase dephosphorylation by PP5.Nature communications · 2023Article
- Plk4 Is a Novel Substrate of Protein Phosphatase 5.International journal of molecular sciences · 2023Article
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation.Nature communications · 2022Article
- Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.Nature reviews. Urology · 2022Review
- Heat Shock-Binding Protein 21 Regulates the Innate Immune Response to Viral Infection.Journal of virology · 2022Article
- Assembly mechanism of early Hsp90-Cdc37-kinase complexes.Science advances · 2022Article
- Microcystins can be extracted from Microcystis aeruginosa using amino acid-derived biosurfactants.Environmental science and pollution research international · 2022Article
- Maintaining proteostasis under mechanical stress.EMBO reports · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The serine/threonine phosphatase protein phosphatase 5 (PP5) regulates hormone- and stress-induced cellular signaling by association with the molecular chaperone heat shock protein 90 (Hsp90). PP5-mediated dephosphorylation of the cochaperone Cdc37 is essential for activation of Hsp90-dependent kinases. However, the details of this mechanism remain unknown. We determined the crystal structure of a Cdc37 phosphomimetic peptide bound to the catalytic domain of PP5. The structure reveals PP5 utilization of conserved elements of phosphoprotein phosphatase (PPP) structure to bind substrate and provides a template for many PPP-substrate interactions. Our data show that, despite a highly conserved structure, elements of substrate specificity are determined within the phosphatase catalytic domain itself. Structure-based mutations in vivo reveal that PP5-mediated dephosphorylation is required for kinase and steroid hormone receptor release from the chaperone complex. Finally, our data show that hyper- or hypoactivity of PP5 mutants increases Hsp90 binding to its inhibitor, suggesting a mechanism to enhance the efficacy of Hsp90 inhibitors by regulation of PP5 activity in tumors.
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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.