Megakaryocytes express functional Aurora-B kinase in endomitosis

Endomitosis (EnM) in megakaryocytes (MKs) is characterized by abortion of mitosis in late anaphase and failure of cytokinesis; subsequent reinitiation of DNA synthesis results in polyploidy. Ablation of chromosomal passenger proteins including Aurora-B kinase causes defects in late anaphase and cyto...

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Bibliographic Details
Published in:Blood 2004-08, Vol.104 (4), p.1017-1024
Main Authors: Geddis, Amy E., Kaushansky, Kenneth
Format: Article
Language:English
Subjects:
Anaphase
Animals
Aurora Kinase A
Aurora Kinase B
Aurora Kinases
Biological and medical sciences
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
Centromere - metabolism
Chromosomal Proteins, Non-Histone - metabolism
Fundamental and applied biological sciences. Psychology
Humans
Inhibitor of Apoptosis Proteins
Megakaryocytes - cytology
Megakaryocytes - enzymology
Mice
Microtubule-Associated Proteins - metabolism
Mitosis
Molecular and cellular biology
Neoplasm Proteins
Phosphorylation
Polyploidy
Protein Binding
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Protein-Serine-Threonine Kinases - physiology
Survivin
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Summary:Endomitosis (EnM) in megakaryocytes (MKs) is characterized by abortion of mitosis in late anaphase and failure of cytokinesis; subsequent reinitiation of DNA synthesis results in polyploidy. Ablation of chromosomal passenger proteins including Aurora-B kinase causes defects in late anaphase and cytokinesis in diploid cells; thus one hypothesis is that the expression or function of these proteins in polyploid MKs is abnormal. It has been reported that Aurora-B kinase mRNA is decreased in polyploid megakaryocytic cells, suggesting that deficiency of Aurora-B kinase is responsible for EnM. We examined the localization of Aurora-B kinase and additional members of the chromosomal passenger protein and aurora kinase families in MKs. We found that in EnM MKs (1) Aurora-B kinase is present and appropriately localized to centromeres in early EnM; (2) in low-ploidy human MKs, centromeric localization of survivin and inner centromere protein (INCENP) can also be demonstrated; (3) the function of Aurora-B kinase, as measured by Ser10 phosphorylation of histone H3, is intact; and (4) aurora-A kinase localizes appropriately to centrosomes in EnM. These results suggest that EnM MKs appropriately express functional Aurora-B kinase and related proteins in early anaphase, making a simple deficiency of this protein an unlikely explanation for polyploidy in this cell type.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2004-02-0419