RNA interference-mediated silencing of mitotic kinesin KIF14 disrupts cell cycle progression and induces cytokinesis failure.

Abstract:

:KIF14 is a microtubule motor protein whose elevated expression is associated with poor-prognosis breast cancer. Here we demonstrate KIF14 accumulation in mitotic cells, where it associated with developing spindle poles and spindle microtubules. Cells at later stages of mitosis were characterized by the concentration of KIF14 at the midbody. Time-lapse microscopy revealed that strong RNA interference (RNAi)-mediated silencing of KIF14 induced cytokinesis failure, causing several rounds of endoreduplication and resulting in multinucleated cells. Additionally, less efficacious KIF14-specific short interfering RNAs (siRNAs) induced multiple phenotypes, all of which resulted in acute apoptosis. Our data demonstrate the ability of siRNA-mediated silencing to generate epiallelic hypomorphs associated with KIF14 depletion. Furthermore, the link we observed between siRNA efficacy and phenotypic outcome indicates that distinct stages during cell cycle progression are disrupted by the differential modulation of KIF14 expression.

journal_name

Mol Cell Biol

authors

Carleton M,Mao M,Biery M,Warrener P,Kim S,Buser C,Marshall CG,Fernandes C,Annis J,Linsley PS

doi

10.1128/MCB.26.10.3853-3863.2006

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

3853-63

issue

10

eissn

0270-7306

issn

1098-5549

pii

26/10/3853

journal_volume

26

pub_type

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