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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3717-3726. Prepublished online as a Blood First Edition Paper on January 29, 2004; DOI 10.1182/blood-2003-09-3365. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-09-3365v1 103/10/3717    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, Y. Articles by Ravid, K. Search for Related Content PubMed PubMed Citation Articles by Zhang, Y. Articles by Ravid, K. Related Collections Hematopoiesis and Stem Cells Neoplasia Cell Cycle Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Aberrant quantity and localization of Aurora-B/AIM-1 and survivin during megakaryocyte polyploidization and the consequences of Aurora-B/AIM-1–deregulated expression Ying Zhang, Yuka Nagata, Guangyao Yu, Hao G. Nguyen, Matthew R. Jones, Paul Toselli, Carl W. Jackson, Masaaki Tatsuka, Kazuo Todokoro, and Katya Ravid From the Departments of Biochemistry and Pharmacology, Whitaker Cardiovascular Institute, Boston University School of Medicine, MA; Recognition and Formation, Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency; Cell Fate Signaling Research Unit, RIKEN (The Institute of Physical and Chemical Research), Wako, Saitama, Japan; St Jude Children's Research Hospital, Memphis, TN; and the Department of Molecular Radiobiology, Hiroshima University, Japan. Megakaryocytes skip late anaphase and cytokinesis during endomitosis. We found normal expression and localization of a fundamental regulator of mitosis, Aurora-B/AIM-1, during prophase in polyploidizing mouse bone marrow megakaryocytes. At late anaphase, however, Aurora-B/AIM-1 is absent or mislocalized. Megakaryocytes treated with a proteasome inhibitor display Aurora-B/AIM-1 properly expressed and localized to the midzone, suggesting that protein degradation contributes to this atypical appearance. In contrast, survivin, an Aurora-B/AIM-1 coregulator of mitosis, is not detected at any stage of the endomitotic cell cycle, and in most megakaryocytes proteasome inhibition does not rescue this phenotype. To further explore the importance of reduced Aurora-B/AIM-1 for polyploidization, it was overexpressed in megakaryocytes of transgenic mice. The phenotype includes increased transgenic mRNA, but not protein, in polyploidy megakaryocytes, further suggesting that Aurora-B/AIM-1 is regulated at the protein level. Aurora-B/AIM-1 protein is, however, elevated in diploid transgenic megakaryocytes. Transgenic mice also exhibit enhanced numbers of megakaryocytes with increased proliferative potential, and some mice exhibit mild decreases in ploidy level. Hence, the molecular programming involved in endomitosis is characterized by the mislocalization or absence of at least 2 critical mitotic regulators, Aurora-B/AIM-1 and survivin. Future studies will examine the impact of survivin restoration on mouse megakaryocyte polyploidization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. J. McCrann, T. Yezefski, H. G. Nguyen, N. Papadantonakis, H. Liu, Q. Wen, J. D. Crispino, and K. Ravid Survivin overexpression alone does not alter megakaryocyte ploidy nor interfere with erythroid/megakaryocytic lineage development in transgenic mice Blood, April 15, 2008; 111(8): 4092 - 4095. [Abstract] [Full Text] [PDF] M. Siatecka, L. Xue, and J. J. Bieker Sumoylation of EKLF Promotes Transcriptional Repression and Is Involved in Inhibition of Megakaryopoiesis Mol. Cell. Biol., December 15, 2007; 27(24): 8547 - 8560. [Abstract] [Full Text] [PDF] C. G. Leung, Y. Xu, B. 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