Source:http://linkedlifedata.com/resource/pubmed/id/20548097
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
13
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pubmed:dateCreated |
2010-10-1
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pubmed:abstractText |
Polyploidization of megakaryocytes (MKs), the platelet precursors, occurs by endomitosis, a mitotic process that fails at late stages of cytokinesis. Expression and function of Aurora B kinase during endomitosis remain controversial. Here, we report that Aurora B is normally expressed during the human MK endomitotic process. Aurora B localized normally in the midzone or midbody during anaphase and telophase in low ploidy megakaryocytes and in up to 16N rare endomitotic MKs was observed. Aurora B was also functional during cytokinesis as attested by phosphorylation of both its activation site and MgcRacGAP, its main substrate. However, despite its activation, Aurora B did not prevent furrow regression. Inhibition of Aurora B by AZD1152-HQPA decreased cell cycle entry both in 2N to 4N and polyploid MKs and induced apoptosis mainly in 2N to 4N cells. In both MK classes, AZD1152-HQPA induced p53 activation and retinoblastoma hypophosphorylation. Resistance of polyploid MKs to apoptosis correlated to a high BclxL level. Aurora B inhibition did not impair MK polyploidization but profoundly modified the endomitotic process by inducing a mis-segregation of chromosomes and a mitotic failure in anaphase. This indicates that Aurora B is dispensable for MK polyploidization but is necessary to achieve a normal endomitotic process.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BIRC5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/aurora kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1528-0020
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pubmed:author |
pubmed-author:AuradeFrédéricF,
pubmed-author:ChangYunhuaY,
pubmed-author:DebiliNajetN,
pubmed-author:GarçonLoïcL,
pubmed-author:JalilAbdelaliA,
pubmed-author:KawashimaToshiyukiT,
pubmed-author:KitamuraToshioT,
pubmed-author:LécluseYannY,
pubmed-author:LarbretFrédéricF,
pubmed-author:LargheroJérômeJ,
pubmed-author:LordierLarissaL,
pubmed-author:VainchenkerWilliamW
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pubmed:issnType |
Electronic
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pubmed:day |
30
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pubmed:volume |
116
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2345-55
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:20548097-Apoptosis,
pubmed-meshheading:20548097-Chromosome Segregation,
pubmed-meshheading:20548097-G1 Phase,
pubmed-meshheading:20548097-Humans,
pubmed-meshheading:20548097-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:20548097-Megakaryocytes,
pubmed-meshheading:20548097-Microtubule-Associated Proteins,
pubmed-meshheading:20548097-Mitosis,
pubmed-meshheading:20548097-Mitotic Spindle Apparatus,
pubmed-meshheading:20548097-Polyploidy,
pubmed-meshheading:20548097-Protein Kinase Inhibitors,
pubmed-meshheading:20548097-Protein-Serine-Threonine Kinases,
pubmed-meshheading:20548097-S Phase
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pubmed:year |
2010
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pubmed:articleTitle |
Aurora B is dispensable for megakaryocyte polyploidization, but contributes to the endomitotic process.
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pubmed:affiliation |
INSERM U1009, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif, France.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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