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Blood, 15 September 2006, Vol. 108, No. 6, pp. 1932-1940. Prepublished online as a Blood First Edition Paper on April 6, 2006; DOI 10.1182/blood-2005-11-4404. This Article Full Text (PDF) All Versions of this Article: 2005-11-4404v1 108/6/1932    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 Mansouri, M. Articles by Fruh, K. Search for Related Content PubMed PubMed Citation Articles by Mansouri, M. Articles by Fruh, K. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 8, 2005 Accepted March 11, 2006 Kaposi's sarcoma herpesvirus K5 eliminates CD31/PECAM from endothelial cells Mandana Mansouri, Janet Douglas, Patrick P Rose, Kristine Gouveia, Gary Thomas, Robert E Means, Ashlee V Moses, and Klaus Fruh* Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, USA Volume Institute, Oregon Health and Science University, Portland, Oregon, USA Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA * Corresponding author; email: fruehk{at}ohsu.edu. The transmembrane ubiquitin ligase K5/MIR2 of Kaposi's sarcoma herpesvirus (KSHV) mediates internalization and lysosomal degradation of glycoproteins involved in antigen presentation and co-stimulation. In endothelial cells (ECs), K5 additionally reduced expression of CD31/PECAM, an adhesion molecule regulating cell-cell interactions of ECs, platelets, monocytes and T cells. K5 also reduced EC migration, a CD31-dependent process. Unlike other K5 substrates, both newly synthesized and pre-existing CD31 molecules were targeted by K5. K5 was transported to the cell surface and ubiquitinated pre-existing CD31 resulting in endocytosis and lysosomal degradation. In the endoplasmic reticulum, newly synthesized CD31 was degraded by proteasomes which required binding of phosphofurin acidic cluster sorting protein-2 (PACS-2) to acidic residues in the carboxyterminal tail of K5. Thus, CD31, a novel target of K5, is efficiently removed from ECs by a dual degradation mechanism that is regulated by the subcellular sorting of the ubiquitin ligase. K5-mediated degradation of CD31 is likely to affect EC function in KS tumors CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: KSHV wages a 2-front war on PECAM/CD31 Robert Yarchoan and Muzammel Haque Blood 2006 108: 1790-1791. [Full Text] [PDF] This article has been cited by other articles: M. Jabbour, E. M. Campbell, H. Fares, and L. Lybarger Discrete Domains of MARCH1 Mediate Its Localization, Functional Interactions, and Posttranscriptional Control of Expression J. Immunol., November 15, 2009; 183(10): 6500 - 6512. [Abstract] [Full Text] [PDF] M. Mansouri, K. Viswanathan, J. L. Douglas, J. Hines, J. Gustin, A. V. Moses, and K. Fruh Molecular Mechanism of BST2/Tetherin Downregulation by K5/MIR2 of Kaposi's Sarcoma-Associated Herpesvirus J. Virol., October 1, 2009; 83(19): 9672 - 9681. [Abstract] [Full Text] [PDF] M. Mansouri, P. P. Rose, A. V. Moses, and K. Fruh Remodeling of Endothelial Adherens Junctions by Kaposi's Sarcoma-Associated Herpesvirus J. Virol., October 1, 2008; 82(19): 9615 - 9628. [Abstract] [Full Text] [PDF] K. M. Atkins, L. Thomas, R. T. Youker, M. J. Harriff, F. Pissani, H. You, and G. Thomas HIV-1 Nef Binds PACS-2 to Assemble a Multikinase Cascade That Triggers Major Histocompatibility Complex Class I (MHC-I) Down-regulation: ANALYSIS USING SHORT INTERFERING RNA AND KNOCK-OUT MICE J. Biol. Chem., April 25, 2008; 283(17): 11772 - 11784. [Abstract] [Full Text] [PDF] K. Cadwell and L. Coscoy The Specificities of Kaposi's Sarcoma-Associated Herpesvirus-Encoded E3 Ubiquitin Ligases Are Determined by the Positions of Lysine or Cysteine Residues within the Intracytoplasmic Domains of Their Targets J. Virol., April 15, 2008; 82(8): 4184 - 4189. [Abstract] [Full Text] [PDF] M. Thomas, J. M. Boname, S. Field, S. Nejentsev, M. Salio, V. Cerundolo, M. Wills, and P. J. Lehner Down-regulation of NKG2D and NKp80 ligands by Kaposi's sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity PNAS, February 5, 2008; 105(5): 1656 - 1661. [Abstract] [Full Text] [PDF] R. E. Means, S. M. Lang, and J. U. Jung The Kaposi's Sarcoma-Associated Herpesvirus K5 E3 Ubiquitin Ligase Modulates Targets by Multiple Molecular Mechanisms J. Virol., June 15, 2007; 81(12): 6573 - 6583. [Abstract] [Full Text] [PDF] L. A. Adang, C. Tomescu, W. K. Law, and D. H. Kedes Intracellular Kaposi's Sarcoma-Associated Herpesvirus Load Determines Early Loss of Immune Synapse Components J. Virol., May 15, 2007; 81(10): 5079 - 5090. [Abstract] [Full Text] [PDF] Q. Li, R. Means, S. Lang, and J. U. Jung Downregulation of Gamma Interferon Receptor 1 by Kaposi's Sarcoma-Associated Herpesvirus K3 and K5 J. Virol., March 1, 2007; 81(5): 2117 - 2127. [Abstract] [Full Text] [PDF]

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