Evidence map›Paper›PMID 37653169›Full record

ArticleNature chemical biology2023

Activity-based profiling of cullin-RING E3 networks by conformation-specific probes.

Lukas T Henneberg, Jaspal Singh, David M Duda, Kheewoong Baek, David Yanishevski, Peter J Murray, Matthias Mann, Sachdev S Sidhu, Brenda A Schulman

Open access · hybridAbstract read
In one paragraph

Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.0field-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

20 citing papers in PubMed, 26 citations in OpenAlex.

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  13. Article
  14. A Kinetic Scout Approach Accelerates Targeted Protein Degrader Development.Angewandte Chemie (International ed. in English) · 2025
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 4 countries.

Lukas T Henneberg *Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0003-3477-4541
Jaspal Singh *School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.
David M Duda *Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Kheewoong BaekDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0002-6853-4936
David YanishevskiDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Peter J MurrayImmunoregulation, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0001-6329-9802
Matthias MannDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0003-1292-4799
Sachdev S SidhuSchool of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada. sachdev.sidhu@uwaterloo.ca.ORCID 0000-0001-7755-5918
Brenda A SchulmanDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany. schulman@biochem.mpg.de.ORCID 0000-0002-3083-1126
Max Planck Institute of Biochemistry · DESt. Jude Children's Research Hospital · USUniversity of Waterloo · CAUniversity of Copenhagen · DK

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
NCI NIH HHS P30 CA021765NIGMS NIH HHS R01 GM129325
6 · The paper itself

Abstract

The cullin-RING ubiquitin ligase (CRL) network comprises over 300 unique complexes that switch from inactive to activated conformations upon site-specific cullin modification by the ubiquitin-like protein NEDD8. Assessing cellular repertoires of activated CRL complexes is critical for understanding eukaryotic regulation. However, probes surveying networks controlled by site-specific ubiquitin-like protein modifications are lacking. We developed a synthetic antibody recognizing the active conformation of NEDD8-linked cullins. Implementing the probe to profile cellular networks of activated CUL1-, CUL2-, CUL3- and CUL4-containing E3s revealed the complexes responding to stimuli. Profiling several cell types showed their baseline neddylated CRL repertoires vary, and prime efficiency of targeted protein degradation. Our probe also unveiled differential rewiring of CRL networks across distinct primary cell activation pathways. Thus, conformation-specific probes can permit nonenzymatic activity-based profiling across a system of numerous multiprotein complexes, which in the case of neddylated CRLs reveals widespread regulation and could facilitate the development of degrader drugs.

Indexed as

Cullin ProteinsUbiquitin-Protein LigasesNEDD8 ProteinUbiquitinUbiquitinationUbiquitinsCullin ProteinsNEDD8 ProteinUbiquitinUbiquitin-Protein LigasesUbiquitins

Identifiers

PMID37653169
PMCPMC10667097
OpenAlexW4386332801

What OpenQuestion holds

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LicenceCC BY
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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.