Evidence map›Paper›PMID 29053960›Full record

ArticleMolecular cell2017

A General Strategy for Discovery of Inhibitors and Activators of RING and U-box E3 Ligases with Ubiquitin Variants.

Mads Gabrielsen, Lori Buetow, Mark A Nakasone, Syed Feroj Ahmed, Gary J Sibbet, Brian O Smith, Wei Zhang, Sachdev S Sidhu, Danny T Huang

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing 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

45 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Locking CBL TKBD in its native conformation presents a novel therapeutic opportunity in mutant CBL-dependent leukemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  6. Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Praja1 RING-finger E3 ubiquitin ligase is a common suppressor of neurodegenerative disease-associated protein aggregation.Neuropathology : official journal of the Japanese Society of Neuropathology · 2022
    Article
  14. Review
  15. Review
  16. Article
  17. Article
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  19. Article
  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

9 authors at 4 institutions in 2 countries.

Mads GabrielsenCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Lori BuetowCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Mark A NakasoneCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Syed Feroj AhmedCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Gary J SibbetCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Brian O SmithInstitute of Molecular Cell and Systems Biology, University of Glasgow, Glasgow G12 8QQ, UK.
Wei ZhangDonnelly Centre for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S3E1, Canada. Electronic address: wx.zhang@mail.utoronto.ca.
Sachdev S SidhuDonnelly Centre for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S3E1, Canada. Electronic address: sachdev.sidhu@utoronto.ca.
Danny T HuangCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK. Electronic address: d.huang@beatson.gla.ac.uk.
Cancer Research UK Scotland Institute · GBUniversity of Toronto · CACancer Research UK · GBUniversity of Glasgow · GB

Funding

Cancer Research UK 23278European Research Council 647849
6 · The paper itself

Abstract

RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report the development of three ubiquitin variants (UbVs), each binding selectively to the RING or U-box domain of a distinct E3 ligase: monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and biochemical analyses revealed that UbVs specifically inhibited the activity of UBE4B or phosphorylated CBL by blocking the E2∼Ub binding site. Surprisingly, the UbV selective for dimeric XIAP formed a dimer to stimulate E3 activity by stabilizing the closed E2∼Ub conformation. We further verified the inhibitory and stimulatory functions of UbVs in cells. Our work provides a general strategy to inhibit or activate RING/U-box E3 ligases and provides a resource for the research community to modulate these enzymes.

Indexed as

Enzyme ActivatorsEnzyme InhibitorsTumor Suppressor ProteinsUbiquitin-Protein Ligase ComplexesX-Linked Inhibitor of Apoptosis ProteinDrug DiscoveryHEK293 CellsHeLa CellsHumansProtein MultimerizationUbiquitin-Protein LigasesEnzyme ActivatorsEnzyme InhibitorsTumor Suppressor ProteinsUBE4B protein, humanUbiquitin-Protein Ligase ComplexesUbiquitin-Protein LigasesXIAP protein, humanX-Linked Inhibitor of Apoptosis ProteinactivationinhibitionRING E3 ligaseubiquitin variantU-box E3 ligase

Identifiers

PMID29053960
PMCPMC5655547
OpenAlexW2766355785

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.