Document Detail

P21-activated kinase 4 (PAK4) is required for metaphase spindle positioning and anchoring.
MedLine Citation:
PMID:  22450748     Owner:  NLM     Status:  MEDLINE    
The oncogenic kinase PAK4 was recently found to be involved in the regulation of the G1 phase and the G2/M transition of the cell cycle. We have also identified that PAK4 regulates Ran GTPase activity during mitosis. Here, we show that after entering mitosis, PAK4-depleted cells maintain a prolonged metaphase-like state. In these cells, chromosome congression to the metaphase plate occurs with normal kinetics but is followed by an extended period during which membrane blebbing and spindle rotation are observed. These bipolar PAK4-depleted metaphase-like spindles have a defective astral microtubule (MT) network and are not centered in the cell but are in close contact with the cell cortex. As the metaphase-like state persists, centrosome fragmentation occurs, chromosomes scatter from the metaphase plate and move toward the spindle poles with an active spindle assembly checkpoint, a phenotype that is reminiscent of cohesion fatigue. PAK4 also regulates the acto-myosin cytoskeleton and we report that PAK4 depletion results in the induction of cortical membrane blebbing during prometaphase arrest. However, we show that membrane blebs, which are strongly enriched in phospho-cofilin, are not responsible for the poor anchoring of the spindle. As PAK4 depletion interferes with the localization of components of the dynein/dynactin complexes at the kinetochores and on the astral MTs, we propose that loss of PAK4 could induce a change in the activities of motor proteins.
G Bompard; G Rabeharivelo; J Cau; A Abrieu; C Delsert; N Morin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-26
Journal Detail:
Title:  Oncogene     Volume:  32     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-14     Completed Date:  2013-04-12     Revised Date:  2014-05-20    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  910-9     Citation Subset:  IM    
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MeSH Terms
Cell Cycle / genetics
Centrosome / metabolism
Chromosome Segregation / drug effects,  genetics,  physiology
Cytoplasm / metabolism
Green Fluorescent Proteins / genetics,  metabolism
HeLa Cells
Kinetochores / metabolism
Metaphase* / drug effects,  genetics,  physiology
Microtubules / drug effects,  metabolism
RNA, Small Interfering / pharmacology
Spindle Apparatus / drug effects,  genetics,  metabolism*,  physiology
p21-Activated Kinases / antagonists & inhibitors,  genetics,  metabolism,  physiology*
Reg. No./Substance:
0/RNA, Small Interfering; 147336-22-9/Green Fluorescent Proteins; EC protein, human; EC Kinases
Comment In:
Bioarchitecture. 2012 Jul-Aug;2(4):130-3   [PMID:  22960742 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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