Evidence map›Paper›PMID 33015833›Full record

ArticleThe EMBO journal2020

Who with whom: functional coordination of E2 enzymes by RING E3 ligases during poly-ubiquitylation.

Christian Lips, Tobias Ritterhoff, Annika Weber, Maria K Janowska, Mandy Mustroph, Thomas Sommer, Rachel E Klevit

Abstract read
In one paragraph

Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
–field-weighted citation impact
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

36 citing papers in PubMed.

  1. Article
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  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. "Design principles of a membrane-spanning ubiquitin ligase".bioRxiv : the preprint server for biology · 2025
    Article
  10. Article
  11. PathogenicThe journal of physical chemistry. B · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025
    Review
  16. Article
  17. Article
  18. Article
  19. The ubiquitin E3 ligase BFAR promotes degradation of PNPLA3.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  20. Article
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

7 authors.

Christian Lips *Max Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch, Germany.
Tobias Ritterhoff *Department of Biochemistry, School of Medicine, University of Washington, Seattle, WA, USA.
Annika WeberMax Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch, Germany.
Maria K JanowskaDepartment of Biochemistry, School of Medicine, University of Washington, Seattle, WA, USA.
Mandy MustrophMax Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch, Germany.
Thomas SommerMax Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch, Germany.
Rachel E KlevitDepartment of Biochemistry, School of Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0002-3476-969X

Funding

Structural and Functional Characterization of BRCA1/BARD1R01GM088055 · NIGMS · UNIVERSITY OF WASHINGTON · PI KLEVIT, RACHEL E · 2009 to 2020
$6.5M
Deutsche Forschungsgemeinschaft (DFG) RI 2874/1-1Deutsche Forschungsgemeinschaft (DFG) SFB 740/TP B05Deutsche Forschungsgemeinschaft (DFG) SPP 1365NIGMS NIH HHS R01 GM088055
6 · The paper itself

Abstract

Protein modification with poly-ubiquitin chains is a crucial process involved in a myriad of cellular pathways. Chain synthesis requires two steps: substrate modification with ubiquitin (priming) followed by repetitive ubiquitin-to-ubiquitin attachment (elongation). RING-type E3 ligases catalyze both reactions in collaboration with specific priming and elongating E2 enzymes. We provide kinetic insight into poly-ubiquitylation during protein quality control by showing that priming is the rate-determining step in protein degradation as directed by the yeast ERAD RING E3 ligases, Hrd1 and Doa10. Doa10 cooperates with the dedicated priming E2, Ubc6, while both E3s use Ubc7 for elongation. Here, we provide direct evidence that Hrd1 uses Ubc7 also for priming. We found that Ubc6 has an unusually high basal activity that does not require strong stimulation from an E3. Doa10 exploits this property to pair with Ubc6 over Ubc7 during priming. Our work not only illuminates the mechanisms of specific E2/E3 interplay in ERAD, but also offers a basis to understand how RING E3s may have properties that are tailored to pair with their preferred E2s.

Indexed as

HumansPoly APolyubiquitinProtein Processing, Post-TranslationalProteolysisSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitinUbiquitinationUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesHRD1 protein, S cerevisiaePoly APolyubiquitinSaccharomyces cerevisiae ProteinsUBC6 protein, S cerevisiaeUBC7 protein, S cerevisiaeUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesE2 conjugating enzymeER-associated protein degradationlinchpinRING E3 ligaseubiquitin

Identifiers

PMID33015833
PMCPMC7667886

What OpenQuestion holds

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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.