title: Megakaryocytes express functional Aurora-B kinase in endomitosis.
abstract: 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.
authors.affiliation: Division of Pediatric Hematology-Oncology, University of California San Diego (UCSD), 9500 Gilman Dr, Mailcode 0665, La Jolla, CA 92093, USA. ageddis@ucsd.edu
authors.forename: Amy E
authors.initials: AE
authors.lastname: Geddis
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kaushansky
mesh_terms: D000705:Anaphase; D000818:Animals; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002503:Centromere / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008533:Megakaryocytes / Q000166:cytology* / Q000201:enzymology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D009363:Neoplasm Proteins; D010766:Phosphorylation; D011123:Polyploidy; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; C513185:Incenp protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; C576921:AURKB protein, human; C576918:Aurka protein, mouse; C576924:Aurkb protein, mouse; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases