Evidence map›Paper›PMID 25383541›Full record

ArticleNature2015

The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C.

Daisuke Izawa, Jonathon Pines

Abstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed
10.2field-weighted citation impact, top 1% 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

135 citing papers in PubMed, 213 citations in OpenAlex.

  1. Article
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  14. The Mitotic Checkpoint Complex controls the association of Cdc20 regulatory protein with the ubiquitin ligase APC/C in mitosis.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  16. The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024
    Review
  17. Article
  18. Review
  19. Article
  20. Article

75 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

2 authors at 1 institution in 1 country.

Daisuke IzawaThe Gurdon Institute and Department of Zoology, Tennis Court Road, Cambridge CB2 1QN, UK.
Jonathon PinesThe Gurdon Institute and Department of Zoology, Tennis Court Road, Cambridge CB2 1QN, UK.
Wellcome/Cancer Research UK Gurdon Institute · GB

Funding

Cancer Research UK 13678Cancer Research UK 13959Cancer Research UK A13678Cancer Research UK A13959Wellcome Trust 092096
6 · The paper itself

Abstract

The spindle assembly checkpoint (SAC) maintains genomic stability by delaying chromosome segregation until the last chromosome has attached to the mitotic spindle. The SAC prevents the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase from recognizing cyclin B and securin by catalysing the incorporation of the APC/C co-activator, CDC20, into a complex called the mitotic checkpoint complex (MCC). The SAC works through unattached kinetochores generating a diffusible 'wait anaphase' signal that inhibits the APC/C in the cytoplasm, but the nature of this signal remains a key unsolved problem. Moreover, the SAC and the APC/C are highly responsive to each other: the APC/C quickly targets cyclin B and securin once all the chromosomes attach in metaphase, but is rapidly inhibited should kinetochore attachment be perturbed. How this is achieved is also unknown. Here, we show that the MCC can inhibit a second CDC20 that has already bound and activated the APC/C. We show how the MCC inhibits active APC/C and that this is essential for the SAC. Moreover, this mechanism can prevent anaphase in the absence of kinetochore signalling. Thus, we propose that the diffusible 'wait anaphase' signal could be the MCC itself, and explain how reactivating the SAC can rapidly inhibit active APC/C.

Indexed as

MitosisAnaphaseAnaphase-Promoting Complex-CyclosomeAnimalsCdc20 ProteinsCytoplasmHeLa CellsHumansM Phase Cell Cycle CheckpointsMultiprotein ComplexesProtein BindingProtein Serine-Threonine KinasesProtein Structure, TertiarySpindle ApparatusSubstrate SpecificityAnaphase-Promoting Complex-CyclosomeBUB1 protein, humanCdc20 ProteinsMultiprotein ComplexesProtein Serine-Threonine Kinases

Identifiers

PMID25383541
PMCPMC4312099
OpenAlexW2021347119

What OpenQuestion holds

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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.