Evidence map›Paper›PMID 30782962›Full record

ArticleThe EMBO journal2019

Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex.

Gang Zhang, Thomas Kruse, Claudia Guasch Boldú, Dimitriya H Garvanska, Fabian Coscia, Matthias Mann, Marin Barisic, Jakob Nilsson

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

50 citing papers in PubMed, 75 citations in OpenAlex.

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  8. Expression and clinical significance of BUB1 in esophageal cancer.American journal of translational research · 2025
    Article
  9. Generation of Cdc20 RNAi-Sensitive Cell Lines to Study Mitotic Exit.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Gang ZhangNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark gang.zhang@cpr.ku.dk jakob.nilsson@cpr.ku.dk.ORCID 0000-0001-7697-7203
Thomas KruseNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Claudia Guasch BoldúCell Division Laboratory, Danish Cancer Society Research Center, Copenhagen, Denmark.
Dimitriya H GarvanskaNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Fabian CosciaNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Matthias MannNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-1292-4799
Marin BarisicCell Division Laboratory, Danish Cancer Society Research Center, Copenhagen, Denmark.
Jakob NilssonNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark gang.zhang@cpr.ku.dk jakob.nilsson@cpr.ku.dk.ORCID 0000-0003-4100-1125
University of Copenhagen · DKDanish Cancer Society · DKQingdao University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Kinetochore localized Mad1 is essential for generating a "wait anaphase" signal during mitosis, hereby ensuring accurate chromosome segregation. Inconsistent models for the function and quantitative contribution of the two mammalian Mad1 kinetochore receptors: Bub1 and the Rod-Zw10-Zwilch (RZZ) complex exist. By combining genome editing and RNAi, we achieve penetrant removal of Bub1 and Rod in human cells, which reveals that efficient checkpoint signaling depends on the integrated activities of these proteins. Rod removal reduces the proximity of Bub1 and Mad1, and we can bypass the requirement for Rod by tethering Mad1 to kinetochores or increasing the strength of the Bub1-Mad1 interaction. We find that Bub1 has checkpoint functions independent of Mad1 localization that are supported by low levels of Bub1 suggesting a catalytic function. In conclusion, our results support an integrated model for the Mad1 receptors in which the primary role of RZZ is to localize Mad1 at kinetochores to generate the Mad1-Bub1 complex.

Indexed as

KinetochoresM Phase Cell Cycle CheckpointsCell Cycle ProteinsChromosomal Proteins, Non-HistoneHeLa CellsHumansMicrotubule-Associated ProteinsMitosisPolypyrimidine Tract-Binding ProteinProtein BindingProtein Interaction Domains and MotifsProtein Serine-Threonine KinasesSignal TransductionSpindle ApparatusBUB1 protein, humanCell Cycle ProteinsChromosomal Proteins, Non-HistoneMAD1L1 protein, humanMicrotubule-Associated ProteinsPolypyrimidine Tract-Binding ProteinProtein Serine-Threonine KinasesPTBP3 protein, humanZW10 protein, humanZwilch protein, humanBub1CRISPRkinetochoreMad1mitosis

Identifiers

PMID30782962
PMCPMC6443202
OpenAlexW2915473820

What OpenQuestion holds

Textmetadata
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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.