ArticleThe Journal of biological chemistry2014
The molecular chaperone Hsp70 activates protein phosphatase 5 (PP5) by binding the tetratricopeptide repeat (TPR) domain.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026Review
- The Fascinating Intricacy of pSer/Thr-Specific Phosphatases and Their Higher-Order Complexes: Emerging Concepts.Biochemistry · 2025Review
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Identification of phosphatases that dephosphorylate the co-chaperone BAG3.Life science alliance · 2025Article
- Therapeutic targets in diabetic peripheral neuropathy: heat shock proteins.Frontiers in endocrinology · 2025Review
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state.Molecular cell · 2021Article
- Maintaining proteostasis under mechanical stress.EMBO reports · 2021Review
- Structure and function of the co-chaperone protein phosphatase 5 in cancer.Cell stress & chaperones · 2020Review
- Leishmania phosphatase PP5 is a regulator of HSP83 phosphorylation and essential for parasite pathogenicity.Parasitology research · 2018Article
- The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix.Cell chemical biology · 2018Article
- PP5 (PPP5C) is a phosphatase of Dvl2.Scientific reports · 2018Article
- Probing the interaction between the histone methyltransferase/deacetylase subunit RBBP4/7 and the transcription factor BCL11A in epigenetic complexes.The Journal of biological chemistry · 2018Article
- Backbone and methyl resonance assignments of the 42 kDa human Hsc70 nucleotide binding domain in the ADP state.Biomolecular NMR assignments · 2017Article
- The remarkable multivalency of the Hsp70 chaperones.Cell stress & chaperones · 2017Review
- The M. tuberculosis HAD phosphatase (Rv3042c) interacts with host proteins and is inhibited by Clofazimine.Cellular and molecular life sciences : CMLS · 2016Article
- Targeting Allosteric Control Mechanisms in Heat Shock Protein 70 (Hsp70).Current topics in medicinal chemistry · 2016Review
- Knockdown of protein phosphatase 5 inhibits ovarian cancer growthOncology letters · 2016Article
- Specific Binding of Tetratricopeptide Repeat Proteins to Heat Shock Protein 70 (Hsp70) and Heat Shock Protein 90 (Hsp90) Is Regulated by Affinity and Phosphorylation.Biochemistry · 2015Article
- Insights into the key interactions between human protein phosphatase 5 and cantharidin using molecular dynamics and site-directed mutagenesis bioassays.Scientific reports · 2015Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Protein phosphatase 5 (PP5) is auto-inhibited by intramolecular interactions with its tetratricopeptide repeat (TPR) domain. Hsp90 has been shown to bind PP5 to activate its phosphatase activity. However, the functional implications of binding Hsp70 to PP5 are not yet clear. In this study, we find that both Hsp90 and Hsp70 bind to PP5 using a luciferase fragment complementation assay. A fluorescence polarization assay shows that Hsp90 (MEEVD motif) binds to the TPR domain of PP5 almost 3-fold higher affinity than Hsp70 (IEEVD motif). However, Hsp70 binding to PP5 stimulates higher phosphatase activity of PP5 than the binding of Hsp90. We find that PP5 forms a stable 1:1 complex with Hsp70, but the interaction appears asymmetric with Hsp90, with one PP5 binding the dimer. Solution NMR studies reveal that Hsc70 and PP5 proteins are dynamically independent in complex, tethered by a disordered region that connects the Hsc70 core and the IEEVD-TPR contact area. This tethered binding is expected to allow PP5 to carry out multi-site dephosphorylation of Hsp70-bound clients with a range of sizes and shapes. Together, these results demonstrate that Hsp70 recruits PP5 and activates its phosphatase activity which suggests dual roles for PP5 that might link chaperone systems with signaling pathways in cancer and development.
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