Evidence map›Paper›PMID 31746663›Full record

ArticleMolecular biology of the cell2020

Functional characterization of MCAK/Kif2C cancer mutations using high-throughput microscopic analysis.

Mike Wagenbach, Juan Jesus Vicente, Yulia Ovechkina, Sarah Domnitz, Linda Wordeman

Open access · bronzeAbstract read
In one paragraph

Article in Molecular biology of the cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 33% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
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  4. TheLife (Basel, Switzerland) · 2025
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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

5 authors at 1 institution in 1 country.

Mike WagenbachDepartment of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
Juan Jesus VicenteDepartment of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
Yulia OvechkinaDepartment of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
Sarah DomnitzDepartment of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
Linda WordemanDepartment of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
University of Washington · US

Funding

Microtubule Dynamics and Chromosome SegregationR01GM069429 · NIGMS · UNIVERSITY OF WASHINGTON · PI WORDEMAN, LINDA · 2004 to 2020
$5.6M
Microtuble-dependent markers for chromosome instabilityR21CA174527 · NCI · UNIVERSITY OF WASHINGTON · PI WORDEMAN, LINDA · 2014 to 2015
$370k
NCI NIH HHS R21 CA174527NIGMS NIH HHS R01 GM069429
6 · The paper itself

Abstract

The microtubule (MT)-depolymerizing activity of MCAK/Kif2C can be quantified by expressing the motor in cultured cells and measuring tubulin fluorescence levels after enough hours have passed to allow tubulin autoregulation to proceed. This method allows us to score the impact of point mutations within the motor domain. We found that, despite their distinctly different activities, many mutations that impact transport kinesins also impair MCAK/Kif2C's depolymerizing activity. We improved our workflow using CellProfiler to significantly speed up the imaging and analysis of transfected cells. This allowed us to rapidly interrogate a number of MCAK/Kif2C motor domain mutations documented in the cancer database cBioPortal. We found that a large proportion of these mutations adversely impact the motor. Using green fluorescent protein-FKBP-MCAK CRISPR cells we found that one deleterious hot-spot mutation increased chromosome instability in a wild-type (WT) background, suggesting that such mutants have the potential to promote tumor karyotype evolution. We also found that increasing WT MCAK/Kif2C protein levels over that of endogenous MCAK/Kif2C similarly increased chromosome instability. Thus, endogenous MCAK/Kif2C activity in normal cells is tuned to a mean level to achieve maximal suppression of chromosome instability.

Indexed as

MicroscopyAmino Acid SequenceChromosomal InstabilityHCT116 CellsHumansKinesinsModels, MolecularMutationNeoplasmsPoint MutationProtein DomainsKIF2C protein, humanKinesins

Identifiers

PMID31746663
PMCPMC7202071
OpenAlexW2990665792

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.