Evidence map›Paper›PMID 26593036›Full record

ArticleScientific reports2015

The activity of protein phosphatase 5 towards native clients is modulated by the middle- and C-terminal domains of Hsp90.

Veronika Haslbeck, Julia M Eckl, Adrian Drazic, Daniel A Rutz, Oliver R Lorenz, Kerstin Zimmermann, Thomas Kriehuber, Claudia Lindemann, Tobias Madl, Klaus Richter

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 32 citations in OpenAlex.

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  7. Heat Shock Proteins in Benign Prostatic Hyperplasia and Prostate Cancer.International journal of molecular sciences · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Veronika HaslbeckCenter for Integrated Protein Science Munich at the Department Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
Julia M EcklCenter for Integrated Protein Science Munich at the Department Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
Adrian DrazicCenter for Integrated Protein Science Munich at the Department Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
Daniel A RutzCenter for Integrated Protein Science Munich at the Department Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
Oliver R LorenzCenter for Integrated Protein Science Munich at the Department Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
Kerstin ZimmermannCenter for Integrated Protein Science Munich at the Department Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
Thomas KriehuberCenter for Integrated Protein Science Munich at the Department Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
Claudia LindemannMedical Proteome Center, Ruhr University Bochum, Universitätsstraße 150, 44780 Bochum, Germany.
Tobias MadlCenter for Integrated Protein Science Munich at the Department Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
Klaus RichterCenter for Integrated Protein Science Munich at the Department Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
Center for Integrated Protein Science Munich · DETechnical University of Munich · DEHelmholtz Zentrum München · DERuhr University Bochum · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Protein phosphatase 5 is involved in the regulation of kinases and transcription factors. The dephosphorylation activity is modulated by the molecular chaperone Hsp90, which binds to the TPR-domain of protein phosphatase 5. This interaction is dependent on the C-terminal MEEVD motif of Hsp90. We show that C-terminal Hsp90 fragments differ in their regulation of the phosphatase activity hinting to a more complex interaction. Also hydrodynamic parameters from analytical ultracentrifugation and small-angle X-ray scattering data suggest a compact structure for the Hsp90-protein phosphatase 5 complexes. Using crosslinking experiments coupled with mass spectrometric analysis and structural modelling we identify sites, which link the middle/C-terminal domain interface of C. elegans Hsp90 to the phosphatase domain of the corresponding kinase. Studying the relevance of the domains of Hsp90 for turnover of native substrates we find that ternary complexes with the glucocorticoid receptor (GR) are cooperatively formed by full-length Hsp90 and PPH-5. Our data suggest that the direct stimulation of the phosphatase activity by C-terminal Hsp90 fragments leads to increased dephosphorylation rates. These are further modulated by the binding of clients to the N-terminal and middle domain of Hsp90 and their presentation to the phosphatase within the phosphatase-Hsp90 complex.

Indexed as

Amino Acid SequenceAnimalsBinding SitesCaenorhabditis elegansCaenorhabditis elegans ProteinsCrystallography, X-RayFluorescence Resonance Energy TransferGene ExpressionHSP90 Heat-Shock ProteinsHumansMolecular Sequence DataNuclear ProteinsPhosphoprotein PhosphatasesProtein BindingProtein Interaction Domains and MotifsProtein MultimerizationCaenorhabditis elegans ProteinsHSP90 Heat-Shock ProteinsNuclear ProteinsPhosphoprotein Phosphatasesprotein phosphatase 5Receptors, GlucocorticoidRecombinant Proteins

Identifiers

PMID26593036
PMCPMC4655416
OpenAlexW2173585040

What OpenQuestion holds

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Registered trials

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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.