Evidence map›Paper›PMID 26882497›Full record

ArticlePLoS genetics2016

Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC/C and Maintain Spindle Checkpoint Arrests.

Judith Zich, Karen May, Konstantinos Paraskevopoulos, Onur Sen, Heather M Syred, Sjaak van der Sar, Hitesh Patel, James J Moresco, Ali Sarkeshik, John R Yates and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Judith ZichWellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
Karen MayWellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
Konstantinos ParaskevopoulosWellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
Onur SenWellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
Heather M SyredWellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
Sjaak van der SarWellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
Hitesh PatelEdinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
James J MorescoScripps Research Institute, La Jolla, California, United States of America.
Ali SarkeshikScripps Research Institute, La Jolla, California, United States of America.
John R YatesScripps Research Institute, La Jolla, California, United States of America.
Juri RappsilberWellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
Kevin G HardwickWellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
University of Edinburgh · GBScripps Research Institute · USWellcome Centre for Cell Biology · GBEdinburgh Cancer Research · GB

Funding

TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 2012 to 2021
$20.7M
Biotechnology and Biological Sciences Research CouncilNIGMS NIH HHS P41 GM103533Wellcome Trust 083610Wellcome Trust 084229Wellcome Trust 084637Wellcome Trust 091020Wellcome Trust 092076Wellcome Trust 103139/Z/13/Z
6 · The paper itself

Abstract

The spindle checkpoint is a mitotic surveillance system which ensures equal segregation of sister chromatids. It delays anaphase onset by inhibiting the action of the E3 ubiquitin ligase known as the anaphase promoting complex or cyclosome (APC/C). Mad3/BubR1 is a key component of the mitotic checkpoint complex (MCC) which binds and inhibits the APC/C early in mitosis. Mps1(Mph1) kinase is critical for checkpoint signalling and MCC-APC/C inhibition, yet few substrates have been identified. Here we identify Mad3 as a substrate of fission yeast Mps1(Mph1) kinase. We map and mutate phosphorylation sites in Mad3, producing mutants that are targeted to kinetochores and assembled into MCC, yet display reduced APC/C binding and are unable to maintain checkpoint arrests. We show biochemically that Mad3 phospho-mimics are potent APC/C inhibitors in vitro, demonstrating that Mad3p modification can directly influence Cdc20(Slp1)-APC/C activity. This genetic dissection of APC/C inhibition demonstrates that Mps1(Mph1) kinase-dependent modifications of Mad3 and Mad2 act in a concerted manner to maintain spindle checkpoint arrests.

Indexed as

Cell Cycle CheckpointsAmino Acid SequenceAnaphase-Promoting Complex-CyclosomeCdc20 ProteinsCell Cycle ProteinsMolecular Sequence DataMutationPhosphorylationProtein BindingProtein KinasesSchizosaccharomycesSchizosaccharomyces pombe ProteinsSpindle ApparatusAnaphase-Promoting Complex-CyclosomeCdc20 ProteinsCell Cycle Proteinsmad3 protein, S pombeMph1 protein, S pombeProtein KinasesSchizosaccharomyces pombe Proteinsslp1 protein, S pombe

Identifiers

PMID26882497
PMCPMC4755545
OpenAlexW2337112577

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.