Evidence map›Paper›PMID 29138295›Full record

ArticleScience signaling2017

Generation of specific inhibitors of SUMO-1- and SUMO-2/3-mediated protein-protein interactions using Affimer (Adhiron) technology.

David J Hughes, Christian Tiede, Natalie Penswick, Anna Ah-San Tang, Chi H Trinh, Upasana Mandal, Katarzyna Z Zajac, Thembaninskosi Gaule, Gareth Howell, Thomas A Edwards and 5 more

Abstract read
In one paragraph

Article in Science signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
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  13. Article
  14. Selective Affimers Recognise the BCL-2 Family Proteins BCL-xChembiochem : a European journal of chemical biology · 2021
    Article
  15. Article
  16. Advances in targeted degradation of endogenous proteins.Cellular and molecular life sciences : CMLS · 2019
    Review
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  20. Review
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

15 authors at 2 institutions in 2 countries.

David J HughesSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. djh25@st-andrews.ac.uk d.c.tomlinson@leeds.ac.uk a.whitehouse@leeds.ac.uk.ORCID http://orcid.org/0000-0002-0090-5710
Christian TiedeSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.ORCID http://orcid.org/0000-0003-0280-4005
Natalie PenswickSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Anna Ah-San TangSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.ORCID http://orcid.org/0000-0002-5216-5080
Chi H TrinhSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Upasana MandalSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.ORCID http://orcid.org/0000-0001-6489-0952
Katarzyna Z ZajacBioScreening Technology Group, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.ORCID http://orcid.org/0000-0002-5537-198X
Thembaninskosi GauleAstbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.ORCID http://orcid.org/0000-0003-2859-4093
Gareth HowellSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.ORCID http://orcid.org/0000-0002-3552-1274
Thomas A EdwardsSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Jianxin DuanSchrödinger GmbH, Mannheim, Germany.
Eric FeyfantSchrödinger Inc., Cambridge, MA 02142, USA.ORCID http://orcid.org/0000-0002-1930-1300
Michael J McPhersonSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.ORCID http://orcid.org/0000-0002-0719-6427
Darren C TomlinsonSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. djh25@st-andrews.ac.uk d.c.tomlinson@leeds.ac.uk a.whitehouse@leeds.ac.uk.ORCID http://orcid.org/0000-0003-4134-7484
Adrian WhitehouseSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. djh25@st-andrews.ac.uk d.c.tomlinson@leeds.ac.uk a.whitehouse@leeds.ac.uk.ORCID http://orcid.org/0000-0003-3866-7110
University of Leeds · GBSchrodinger (United States) · US

Funding

Biotechnology and Biological Sciences Research Council BB/M006557/1Wellcome Trust 089330
6 · The paper itself

Abstract

Because protein-protein interactions underpin most biological processes, developing tools that target them to understand their function or to inform the development of therapeutics is an important task. SUMOylation is the posttranslational covalent attachment of proteins in the SUMO family (SUMO-1, SUMO-2, or SUMO-3), and it regulates numerous cellular pathways. SUMOylated proteins are recognized by proteins with SUMO-interaction motifs (SIMs) that facilitate noncovalent interactions with SUMO. We describe the use of the Affimer system of peptide display for the rapid isolation of synthetic binding proteins that inhibit SUMO-dependent protein-protein interactions mediated by SIMs both in vitro and in cells. Crucially, these synthetic proteins did not prevent SUMO conjugation either in vitro or in cell-based systems, enabling the specific analysis of SUMO-mediated protein-protein interactions. Furthermore, through structural analysis and molecular modeling, we explored the molecular mechanisms that may underlie their specificity in interfering with either SUMO-1-mediated interactions or interactions mediated by either SUMO-2 or SUMO-3. Not only will these reagents enable investigation of the biological roles of SUMOylation, but the Affimer technology used to generate these synthetic binding proteins could also be exploited to design or validate reagents or therapeutics that target other protein-protein interactions.

Indexed as

Peptide LibraryFluorescent Antibody TechniqueHEK293 CellsHumansModels, MolecularMolecular Dynamics SimulationPeptide FragmentsProtein Interaction Domains and MotifsSmall Molecule LibrariesSmall Ubiquitin-Related Modifier ProteinsSUMO-1 ProteinSumoylationUbiquitinsPeptide FragmentsPeptide LibrarySmall Molecule LibrariesSmall Ubiquitin-Related Modifier ProteinsSUMO-1 ProteinSUMO2 protein, humanSUMO3 protein, humanUbiquitins

Identifiers

PMID29138295
PMCPMC5777597
OpenAlexW2769000880

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.