Evidence map›Paper›PMID 31511308›Full record

ArticleThe Journal of cell biology2019

Checkpoint signaling and error correction require regulation of the MPS1 T-loop by PP2A-B56.

Daniel Hayward, James Bancroft, Davinderpreet Mangat, Tatiana Alfonso-Pérez, Sholto Dugdale, Julia McCarthy, Francis A Barr, Ulrike Gruneberg

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2019. 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
3.9field-weighted citation impact, top 6% 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, 43 citations in OpenAlex.

  1. Structure and function of the outer kinetochore.Nature reviews. Molecular cell biology · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Principles and dynamics of spindle assembly checkpoint signalling.Nature reviews. Molecular cell biology · 2023
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Spindle assembly checkpoint activation and silencing at kinetochores.Seminars in cell & developmental biology · 2021
    Review
  15. PP2A Phosphatase as an Emerging Viral Host Factor.Frontiers in cellular and infection microbiology · 2021
    Review
  16. Article
  17. Article
  18. Phospho-regulation of mitotic spindle assembly.Cytoskeleton (Hoboken, N.J.) · 2020
    Review
  19. Article
  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

8 authors at 1 institution in 1 country.

Daniel HaywardSir William Dunn School of Pathology, University of Oxford, Oxford, UK.ORCID 0000-0003-0736-0116
James BancroftSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Davinderpreet Mangat *Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Tatiana Alfonso-Pérez *Department of Biochemistry, University of Oxford, Oxford, UK.ORCID 0000-0003-1421-9217
Sholto DugdaleSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Julia McCarthySir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Francis A BarrDepartment of Biochemistry, University of Oxford, Oxford, UK.ORCID 0000-0001-7518-253X
Ulrike GrunebergSir William Dunn School of Pathology, University of Oxford, Oxford, UK ulrike.gruneberg@path.ox.ac.uk.ORCID 0000-0001-8344-0500
University of Oxford · GB

Funding

Biotechnology and Biological Sciences Research Council BB/M00354X/1Cancer Research UK 15940Cancer Research UK 24743Medical Research Council MR/K006703/1
6 · The paper itself

Abstract

During mitosis, the formation of microtubule-kinetochore attachments is monitored by the serine/threonine kinase monopolar spindle 1 (MPS1). MPS1 is recruited to unattached kinetochores where it phosphorylates KNL1, BUB1, and MAD1 to initiate the spindle assembly checkpoint. This arrests the cell cycle until all kinetochores have been stably captured by microtubules. MPS1 also contributes to the error correction process rectifying incorrect kinetochore attachments. MPS1 activity at kinetochores requires autophosphorylation at multiple sites including threonine 676 in the activation segment or "T-loop." We now demonstrate that the BUBR1-bound pool of PP2A-B56 regulates MPS1 T-loop autophosphorylation and hence activation status in mammalian cells. Overriding this regulation using phosphomimetic mutations in the MPS1 T-loop to generate a constitutively active kinase results in a prolonged mitotic arrest with continuous turnover of microtubule-kinetochore attachments. Dynamic regulation of MPS1 catalytic activity by kinetochore-localized PP2A-B56 is thus critical for controlled MPS1 activity and timely cell cycle progression.

Indexed as

Signal TransductionCell Cycle ProteinsCells, CulturedHEK293 CellsHeLa CellsHumansProtein Phosphatase 2Protein Serine-Threonine KinasesProtein-Tyrosine KinasesCell Cycle ProteinsPP2A-B56alpha protein, humanProtein Phosphatase 2Protein Serine-Threonine KinasesProtein-Tyrosine KinasesTTK protein, human

Identifiers

PMID31511308
PMCPMC6781431
OpenAlexW2973032422

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.