Evidence map›Paper›PMID 24695856›Full record

ArticleJournal of cell science2014

Multisite phosphorylation of C-Nap1 releases it from Cep135 to trigger centrosome disjunction.

Tara Hardy, Miseon Lee, Rebecca S Hames, Suzanna L Prosser, Donna-Marie Cheary, Mugdha D Samant, Francisca Schultz, Joanne E Baxter, Kunsoo Rhee, Andrew M Fry

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.2field-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

37 citing papers in PubMed, 72 citations in OpenAlex.

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  15. Phospho-regulation of mitotic spindle assembly.Cytoskeleton (Hoboken, N.J.) · 2020
    Review
  16. Article
  17. Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  18. The Journal of biological chemistry · 2020
    Article
  19. Article
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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

10 authors at 2 institutions in 2 countries.

Tara HardyDepartment of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
Miseon LeeDepartment of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
Rebecca S HamesDepartment of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
Suzanna L ProsserDepartment of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
Donna-Marie ChearyDepartment of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
Mugdha D SamantDepartment of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
Francisca SchultzDepartment of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
Joanne E BaxterDepartment of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
Kunsoo RheeDepartment of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
Andrew M FryDepartment of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK amf5@le.ac.uk.
University of Leicester · GBSeoul National University · KR

Funding

Biotechnology and Biological Sciences Research Council BB/C000013/1Cancer Research UKWellcome Trust 082828
6 · The paper itself

Abstract

During mitotic entry, centrosomes separate to establish the bipolar spindle. Delays in centrosome separation can perturb chromosome segregation and promote genetic instability. However, interphase centrosomes are physically tethered by a proteinaceous linker composed of C-Nap1 (also known as CEP250) and the filamentous protein rootletin. Linker disassembly occurs at the onset of mitosis in a process known as centrosome disjunction and is triggered by the Nek2-dependent phosphorylation of C-Nap1. However, the mechanistic consequences of C-Nap1 phosphorylation are unknown. Here, we demonstrate that Nek2 phosphorylates multiple residues within the C-terminal domain of C-Nap1 and, collectively, these phosphorylation events lead to loss of oligomerization and centrosome association. Mutations in non-phosphorylatable residues that make the domain more acidic are sufficient to release C-Nap1 from the centrosome, suggesting that it is an increase in overall negative charge that is required for this process. Importantly, phosphorylation of C-Nap1 also perturbs interaction with the core centriolar protein, Cep135, and interaction of endogenous C-Nap1 and Cep135 proteins is specifically lost in mitosis. We therefore propose that multisite phosphorylation of C-Nap1 by Nek2 perturbs both oligomerization and Cep135 interaction, and this precipitates centrosome disjunction at the onset of mitosis.

Indexed as

AutoantigensCarrier ProteinsCell Cycle ProteinsCentriolesCentrosomeChromosome SegregationCytoskeletal ProteinsGenomic InstabilityHeLa CellsHumansMitosisMutationNIMA-Related KinasesPhosphorylationProtein BindingProtein EngineeringAutoantigensCarrier ProteinsCell Cycle ProteinsCEP135 protein, humanCEP250 protein, humanCROCC protein, humanCytoskeletal ProteinsNEK2 protein, humanNIMA-Related KinasesProtein Serine-Threonine KinasesRNA, Small InterferingCentriolar linkerCentrosome disjunctionCep135C-Nap1Nek2

Identifiers

PMID24695856
PMCPMC4038944
OpenAlexW2150117534

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.