Evidence map›Paper›PMID 24695965›Full record

ArticleChromosoma2014

Conditional targeting of MAD1 to kinetochores is sufficient to reactivate the spindle assembly checkpoint in metaphase.

Timo E F Kuijt, Manja Omerzu, Adrian T Saurin, Geert J P L Kops

Open access · hybridAbstract read
In one paragraph

Article in Chromosoma, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

22 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Chemical tools for dissecting cell division.Nature chemical biology · 2021
    Review
  7. Article
  8. Article
  9. MAD1: Kinetochore Receptors and Catalytic Mechanisms.Frontiers in cell and developmental biology · 2018
    Review
  10. Optogenetic control of kinetochore function.Nature chemical biology · 2017
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Signalling dynamics in the spindle checkpoint response.Nature reviews. Molecular cell biology · 2014
    Review
  20. Review
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

4 authors at 2 institutions in 1 country.

Timo E F KuijtMolecular Cancer Research, University Medical Center Utrecht, 3584 CG, Utrecht, The Netherlands.
Manja Omerzu
Adrian T Saurin
Geert J P L Kops
University Medical Center Utrecht · NLCancer Genomics Centre · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fidelity of chromosome segregation is monitored by the spindle assembly checkpoint (SAC). Key components of the SAC include MAD1, MAD2, BUB1, BUB3, BUBR1, and MPS1. These proteins accumulate on kinetochores in early prometaphase but are displaced when chromosomes attach to microtubules and/or biorient on the mitotic spindle. As a result, stable attachment of the final chromosome satisfies the SAC, permitting activation of the anaphase promoting complex/cyclosome (APC/C) and subsequent anaphase onset. SAC satisfaction is reversible, however, as addition of taxol during metaphase stops cyclin B1 degradation by the APC/C. We now show that targeting MAD1 to kinetochores during metaphase is sufficient to reestablish SAC activity after initial silencing. Using rapamycin-induced heterodimerization of FKBP-MAD1 to FRB-MIS12 and live monitoring of cyclin B1 degradation, we show that timed relocalization of MAD1 during metaphase can stop cyclin B1 degradation without affecting chromosome-spindle attachments. APC/C inhibition represented true SAC reactivation, as FKBP-MAD1 required an intact MAD2-interaction motif and MPS1 activity to accomplish this. Our data show that MAD1 kinetochore localization dictates SAC activity and imply that SAC regulatory mechanisms downstream of MAD1 remain functional in metaphase.

Indexed as

Cell Cycle CheckpointsMetaphaseCell Cycle ProteinsHeLa CellsHumansKinetochoresNuclear ProteinsProtein TransportSpindle ApparatusCell Cycle ProteinsMAD1L1 protein, humanNuclear Proteins

Identifiers

PMID24695965
PMCPMC4169584
OpenAlexW2118989080

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.