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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 (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 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. Social Bookmarking                   What's this? Submitted October 1, 2003 Accepted December 16, 2003 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* Biochemistry, Boston University School of Medicine, Boston, MA, USA Recognition and Formation, Japan Science and Technology Corporation, Wako, Saitama, Japan Medicine, St. Jude Children's Research Hospital, Memphis, TN, USA Molecular Radiobiology, Hiroshima University, Hiroshima, Japan Recognition and Formation, Japan Science and Technology Corporation, Wako, Saitama, Japan; Cell Fate Signaling Research Unit, The institute of Physical and chemical research, Wako, Saitama, Japan * Corresponding author; email: ravid{at}biochem.bumc.bu.edu. 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 co-regulator of mitosis, is not detected at any stage of the endomitotic cell cycle, and proteasome inhibition does not rescue this phenotype in most megakaryocytes. 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 protein level. Aurora-B/AIM-1 protein is, however, elevated in diploid transgenic megakaryocytes. The transgenic mice also exhibit an enhanced number of megakaryocytes with increased proliferative potential, and in some mice, a mild decrease in ploidy level. Hence, the molecular programming involved in endomitosis is characterized by the absence and/or mislocalization of at least two critical mitotic regulators, Aurora-B/AIM-1 and Survivin. Future studies will examine the impact of Survivin restoration on megakaryocyte polyploidization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. G. Nguyen, M. Makitalo, D. Yang, D. Chinnappan, C. St. Hilaire, and K. Ravid Deregulated Aurora-B induced tetraploidy promotes tumorigenesis FASEB J, August 1, 2009; 23(8): 2741 - 2748. [Abstract] [Full Text] [PDF] K. Ravid Megakaryocytes survive without survivin Blood, July 2, 2009; 114(1): 4 - 4. [Abstract] [Full Text] [PDF] Q. Wen, C. Leung, Z. Huang, S. Small, A. L. Reddi, J. D. Licht, and J. D. Crispino Survivin is not required for the endomitotic cell cycle of megakaryocytes Blood, July 2, 2009; 114(1): 153 - 156. [Abstract] [Full Text] [PDF] S. Peddibhotla, M. H. Lam, M. Gonzalez-Rimbau, and J. M. Rosen From the Cover: The DNA-damage effector checkpoint kinase 1 is essential for chromosome segregation and cytokinesis PNAS, March 31, 2009; 106(13): 5159 - 5164. [Abstract] [Full Text] [PDF] L. Lordier, A. Jalil, F. Aurade, F. Larbret, J. Larghero, N. Debili, W. Vainchenker, and Y. Chang Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling Blood, October 15, 2008; 112(8): 3164 - 3174. [Abstract] [Full Text] [PDF] D. J. McCrann, T. Yezefski, H. G. Nguyen, N. Papadantonakis, H. Liu, Q. Wen, J. D. Crispino, and K. 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