Evidence map›Paper›PMID 31455778›Full record

ArticleNature communications2019

Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C.

Suyang Zhang, Thomas Tischer, David Barford

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in Nature communications, 2019. 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
3.3field-weighted citation impact, top 8% 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, 67 citations in OpenAlex.

  1. Article
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  13. Cryo-EM structures of apo-APC/C and APC/CNature communications · 2024
    Article
  14. Article
  15. Article
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  17. APC/C prevents a noncanonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  18. Review
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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

3 authors at 1 institution in 2 countries.

Suyang ZhangMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Thomas TischerMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.ORCID http://orcid.org/0000-0002-6845-2762
David BarfordMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. dbarford@mrc-lmb.cam.ac.uk.ORCID http://orcid.org/0000-0001-8810-950X
MRC Laboratory of Molecular Biology · GB

Funding

Cancer Research UK 14109Cancer Research UK 24307Cancer Research UK C576/A14109Medical Research Council MC_UP_1201/6
6 · The paper itself

Abstract

The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression by controlling the temporal degradation of specific cell cycle regulators. Although cyclin A2 and cyclin B1 are both targeted for degradation by the APC/C, during the spindle assembly checkpoint (SAC), the mitotic checkpoint complex (MCC) represses APC/C's activity towards cyclin B1, but not cyclin A2. Through structural, biochemical and in vivo analysis, we identify a non-canonical D box (D2) that is critical for cyclin A2 ubiquitination in vitro and degradation in vivo. During the SAC, cyclin A2 is ubiquitinated by the repressed APC/C-MCC, mediated by the cooperative engagement of its KEN and D2 boxes, ABBA motif, and the cofactor Cks. Once the SAC is satisfied, cyclin A2 binds APC/C-Cdc20 through two mutually exclusive binding modes, resulting in differential ubiquitination efficiency. Our findings reveal that a single substrate can engage an E3 ligase through multiple binding modes, affecting its degradation timing and efficiency.

Indexed as

Amino Acid MotifsAnaphase-Promoting Complex-CyclosomeCdc20 ProteinsCDC2-CDC28 KinasesCell Cycle ProteinsCryoelectron MicroscopyCyclin A2HEK293 CellsHumansIntravital MicroscopyModels, MolecularM Phase Cell Cycle CheckpointsProtein BindingProteolysisSpindle ApparatusSubstrate SpecificityAnaphase-Promoting Complex-CyclosomeCCNA2 protein, humanCDC20 protein, humanCdc20 ProteinsCDC2-CDC28 KinasesCell Cycle ProteinsCKS2 protein, humanCyclin A2

Identifiers

PMID31455778
PMCPMC6712056
OpenAlexW2971054316

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.