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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1479-1489. Prepublished online as a Blood First Edition Paper on October 12, 2006; DOI 10.1182/blood-2006-02-003749. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2006-02-003749v1 109/4/1479    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 Caldas, H. Articles by Altura, R. A. Search for Related Content PubMed PubMed Citation Articles by Caldas, H. Articles by Altura, R. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Dissecting the role of endothelial SURVIVIN Ex3 in angiogenesis Hugo Caldas1, Jason R. Fangusaro1,3, Daniel R. Boué2,4, Michael P. Holloway1, and Rachel A. Altura1,3 1 Center for Childhood Cancer, 2 Center for Biopathology, Columbus Children's Research Institute, and Departments of3 Pediatrics and 4 Pathology, The Ohio State University, Columbus, OH The identification of alternative splice variants of Survivin that possess distinct functions from those originally identified for the main Survivin isoform has greatly increased the complexity of our understanding of the role of Survivin in different cells. Previous functional studies of the Survivin splice variants have been performed almost exclusively in cancer cells. However, Survivin has increasingly been implicated in other normal physiologic and pathophysiologic processes, including angiogenesis. In this study, we dissect the involvement of Survivin Ex3 in angiogenesis. We show by confocal microscopy that a pool of endothelial Survivin Ex3 is localized to membrane ruffles. We also demonstrate that Survivin Ex3 is the Survivin splice variant responsible for modulating angiogenesis in vitro, in tube formation assays, and in vivo, in an in vivo angiogenesis assay. Our data indicate that Survivin Ex3 may regulate angiogenesis via several mechanisms including cell invasion, migration, and Rac1 activation. Our findings identify a novel pathway regulating angiogenesis through Survivin Ex3 and a novel mechanism for Rac1 activation during angiogenesis. In conclusion, our results provide new insights into the regulation of endothelial cell homeostasis and angiogenesis by the Survivin proteins. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Nakagawa, S. Yasuda, E. Matsuura, K. Kobayashi, M. Ieko, H. Kataoka, T. Horita, T. Atsumi, and T. Koike Nicked {beta}2-glycoprotein I binds angiostatin 4.5 (plasminogen kringle 1-5) and attenuates its antiangiogenic property Blood, September 17, 2009; 114(12): 2553 - 2559. [Abstract] [Full Text] [PDF] H. Hu, Y. Shikama, I. Matsuoka, and J. Kimura Terminally differentiated neutrophils predominantly express Survivin-2{alpha}, a dominant-negative isoform of Survivin J. Leukoc. Biol., February 1, 2008; 83(2): 393 - 400. [Abstract] [Full Text] [PDF] P. Lechler, X. Wu, W. Bernhardt, V. Campean, S. Gastiger, T. Hackenbeck, B. Klanke, A. Weidemann, C. Warnecke, K. Amann, et al. The Tumor Gene Survivin Is Highly Expressed in Adult Renal Tubular Cells: Implications for a Pathophysiological Role in the Kidney Am. J. Pathol., November 1, 2007; 171(5): 1483 - 1498. [Abstract] [Full Text] [PDF]

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