Evidence map›Paper›PMID 23708001›Full record

ArticleNature cell biology2013

Emi1 preferentially inhibits ubiquitin chain elongation by the anaphase-promoting complex.

Weiping Wang, Marc W Kirschner

Abstract read
In one paragraph

Article in Nature cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing 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

44 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Cryo-EM structures of apo-APC/C and APC/CNature communications · 2024
    Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Examining the mechanistic relationship of APC/CProtein science : a publication of the Protein Society · 2022
    Article
  11. Article
  12. The role of Fbxo5 in the development of human malignant tumors.American journal of cancer research · 2022
    Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors.

Weiping WangDepartment of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
Marc W Kirschner

Funding

CELL CYCLE REGULATIONR01GM039023 · NIGMS · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI KIRSCHNER, MARC WALLACE · 1988 to 2017
$10.2M
NIGMS NIH HHS R01 GM039023
6 · The paper itself

Abstract

The anaphase-promoting complex (APC) is the crucial ubiquitin ligase targeting the regulatory machinery of the cell cycle. Emi1, a major modulator of APC activity, is thought to act competitively as a pseudosubstrate. We show that the modulation of APC activity is more subtle: Emi1 inhibits ubiquitylation at both substrate binding and separately at the step of ubiquitin transfer to APC-bound substrates. The zinc-binding region of Emi1 allows multiple monoubiquitylation of substrates, but preferentially suppresses the ubiquitin chain elongation by UBCH10. Furthermore, the carboxy-terminal tail of Emi1 antagonizes chain elongation by Ube2S, by competitively preventing its binding to the APC cullin subunit through electrostatic interaction. Combinatorially, Emi1 effectively stabilizes APC substrates by suppressing ubiquitin chain extension. Deubiquitylating enzymes can then convert inhibited substrates to their basal state. Chain elongation may be a particularly sensitive step for controlling degradation, and this study provides the first kinetic evidence for how it is inhibited.

Indexed as

Adenomatous Polyposis Coli ProteinAnaphase-Promoting Complex-CyclosomeCell CycleCell Cycle ProteinsCell NucleusF-Box ProteinsHeLa CellsHumansImmunoblottingMitosisPeptide Chain Elongation, TranslationalProtein BindingStatic ElectricityUbiquitinUbiquitinationUbiquitin-Conjugating EnzymesAdenomatous Polyposis Coli ProteinAnaphase-Promoting Complex-CyclosomeAPC protein, humanCell Cycle ProteinsF-Box ProteinsFBXO5 protein, humanUBE2C protein, humanUbe2S protein, humanUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligase Complexes

Identifiers

PMID23708001
PMCPMC3812805

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.