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Blood, 15 January 2007, Vol. 109, No. 2, pp. 584-594. Prepublished online as a Blood First Edition Paper on September 26, 2006; DOI 10.1182/blood-2006-03-012013. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-03-012013v1 109/2/584    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 Cayrol, C. Articles by Girard, J.-P. Search for Related Content PubMed PubMed Citation Articles by Cayrol, C. Articles by Girard, J.-P. Related Collections Cell Cycle Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The THAP–zinc finger protein THAP1 regulates endothelial cell proliferation through modulation of pRB/E2F cell-cycle target genes Corinne Cayrol1, Chrystelle Lacroix1, Catherine Mathe1, Vincent Ecochard1, Michele Ceribelli2, Emilie Loreau3, Vladimir Lazar4, Philippe Dessen4, Roberto Mantovani2, Luc Aguilar3, and Jean-Philippe Girard1, 1 Laboratoire de Biologie Vasculaire, Equipe labellisée ‘La Ligue 2006,’ Institut de Pharmacologie et de Biologie Structurale (IPBS), Centre National de la Recherche Scientifique (CNRS) Unité mixte de recherche (UMR) 5089, Toulouse, France; 2 Dipartimento di Scienze Biomolecolari e Biotecnologie, Università di Milano, Milan, Italy; 3 ENDOCUBE, Prologue Biotech, Labège, France; 4 Unité de Génomique Fonctionnelle et Bioinformatique, Institut Gustave Roussy, Villejuif, France We recently cloned a novel human nuclear factor (designated THAP1) from postcapillary venule endothelial cells (ECs) that contains a DNA-binding THAP domain, shared with zebrafish E2F6 and several Caenorhabditis elegans proteins interacting genetically with retinoblastoma gene product (pRB). Here, we show that THAP1 is a physiologic regulator of EC proliferation and cell-cycle progression, 2 essential processes for angiogenesis. Retroviral-mediated gene transfer of THAP1 into primary human ECs inhibited proliferation, and large-scale expression profiling with microarrays revealed that THAP1-mediated growth inhibition is due to coordinated repression of pRB/E2F cell-cycle target genes. Silencing of endogenous THAP1 through RNA interference similarly inhibited EC proliferation and G1/S cell-cycle progression, and resulted in down-regulation of several pRB/E2F cell-cycle target genes, including RRM1, a gene required for S-phase DNA synthesis. Chromatin immunoprecipitation assays in proliferating ECs showed that endogenous THAP1 associates in vivo with a consensus THAP1-binding site found in the RRM1 promoter, indicating that RRM1 is a direct transcriptional target of THAP1. The similar phenotypes observed after THAP1 overexpression and silencing suggest that an optimal range of THAP1 expression is essential for EC proliferation. Together, these data provide the first links in mammals among THAP proteins, cell proliferation, and pRB/E2F cell-cycle pathways. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Bessiere, C. Lacroix, S. Campagne, V. Ecochard, V. Guillet, L. Mourey, F. Lopez, J. Czaplicki, P. Demange, A. Milon, et al. Structure-Function Analysis of the THAP Zinc Finger of THAP1, a Large C2CH DNA-binding Module Linked to Rb/E2F Pathways J. Biol. Chem., February 15, 2008; 283(7): 4352 - 4363. [Abstract] [Full Text] [PDF]

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