Evidence map›Paper›PMID 27312108›Full record

ArticleEMBO reports2016

Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms.

Katja K Dove, Benjamin Stieglitz, Emily D Duncan, Katrin Rittinger, Rachel E Klevit

Open access · bronzeAbstract read
In one paragraph

Article in EMBO reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

65 citing papers in PubMed, 93 citations in OpenAlex.

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  12. Biochemical analysis of PD-L1 ubiquitination by CRL3Structure (London, England : 1993) · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism.International journal of molecular sciences · 2023
    Review

5 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 2 countries.

Katja K DoveDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Benjamin StieglitzMill Hill Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0003-3634-6997
Emily D DuncanDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Katrin RittingerMill Hill Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0002-7698-4435
Rachel E KlevitDepartment of Biochemistry, University of Washington, Seattle, WA, USA klevit@uw.edu.ORCID 0000-0002-3476-969X
University of Washington · USThe Francis Crick Institute · GB

Funding

TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
Structural and Functional Characterization of BRCA1/BARD1R01GM088055 · NIGMS · UNIVERSITY OF WASHINGTON · PI KLEVIT, RACHEL E · 2009 to 2020
$6.5M
Cancer Research UKMedical Research Council U117565398NIGMS NIH HHS R01 GM088055NIGMS NIH HHS T32 GM007270Wellcome Trust
6 · The paper itself

Abstract

RING-in-between-RING (RBR) ubiquitin (Ub) ligases are a distinct class of E3s, defined by a RING1 domain that binds E2 Ub-conjugating enzyme and a RING2 domain that contains an active site cysteine similar to HECT-type E3s. Proposed to function as RING/HECT hybrids, details regarding the Ub transfer mechanism used by RBRs have yet to be defined. When paired with RING-type E3s, E2s perform the final step of Ub ligation to a substrate. In contrast, when paired with RBR E3s, E2s must transfer Ub onto the E3 to generate a E3~Ub intermediate. We show that RBRs utilize two strategies to ensure transfer of Ub from the E2 onto the E3 active site. First, RING1 domains of HHARI and RNF144 promote open E2~Ubs. Second, we identify a Ub-binding site on HHARI RING2 important for its recruitment to RING1-bound E2~Ub. Mutations that ablate Ub binding to HHARI RING2 also decrease RBR ligase activity, consistent with RING2 recruitment being a critical step for the RBR Ub transfer mechanism. Finally, we demonstrate that the mechanism defined here is utilized by a variety of RBRs.

Indexed as

Binding SitesCatalytic DomainHumansHydrophobic and Hydrophilic InteractionsModels, MolecularPolycomb Repressive Complex 1Protein BindingProtein ConformationProtein TransportTumor Suppressor ProteinsUbiquitinUbiquitinationUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesUbiquitin ThiolesteraseBAP1 protein, humanPolycomb Repressive Complex 1RING1 protein, humanTumor Suppressor ProteinsUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesUbiquitin ThiolesteraseHHARIHOIPParkinRBRubiquitin E3 ligase

Identifiers

PMID27312108
PMCPMC4967960
OpenAlexW2444064634

What OpenQuestion holds

Textmetadata
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.