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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2790-2796. Prepublished online as a Blood First Edition Paper on December 6, 2005; DOI 10.1182/blood-2005-07-2744. This Article Full Text (PDF) All Versions of this Article: 2005-07-2744v1 107/7/2790    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 Nachbur, U. Articles by Brunner, T. Search for Related Content PubMed PubMed Citation Articles by Nachbur, U. Articles by Brunner, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 11, 2005 Accepted November 10, 2005 Post-transcriptional regulation of Fas (CD95) ligand killing activity by lipid rafts Ueli Nachbur, Daniela Kassahn, Shida Yousefi, Daniel Legler, and Thomas Brunner* Institute of Pathology, University of Bern, Bern, Switzerland Institute of Pharmacology, University of Bern, Bern, Switzerland Biotechnology Institute Thurgau, University of Konstanz, Taegerwilen, Switzerland * Corresponding author; email: thomas.brunner{at}pathology.unibe.ch. Fas (CD95/Apo-1) ligand-mediated apoptosis induction of target cells is one of the major effector mechanisms by which cytotoxic lymphocytes (T cells and natural killer cells) kill their target cells. In T cells, Fas ligand expression is tightly regulated at a transcriptional level through the activation of a distinct set of transcription factors. Increasing evidence, however, supports an important role for post-transcriptional regulation of Fas ligand expression and activity. Lipid rafts are cholesterol- and sphingolipid-rich membrane microdomains, critically involved in the regulation of membrane receptor signaling complexes through the clustering and concentration of signaling molecules. Here, we now provide evidence that Fas ligand is constitutively localized in lipid rafts of FasL transfectants and primary T cells. Importantly, disruption of lipid rafts strongly reduces the apoptosis-inducing activity of Fas ligand. Localization to lipid rafts appears to be predominantly mediated by the characteristic cytoplasmic proline-rich domain of Fas Ligand, as mutations of this domain result in reduced recruitment to lipid rafts and attenuated Fas ligand killing activity. We conclude that Fas ligand clustering in lipid rafts represents an important control mechanism in the regulation of T cell-mediated cytotoxicity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. G. Atanasov, D. Leiser, C. Roesselet, M. Noti, N. Corazza, K. Schoonjans, and T. Brunner Cell cycle-dependent regulation of extra-adrenal glucocorticoid synthesis in murine intestinal epithelial cells FASEB J, December 1, 2008; 22(12): 4117 - 4125. [Abstract] [Full Text] [PDF] M. Sun, S. Lee, S. Karray, M. Levi-Strauss, K. T. Ames, and P. J. Fink Cutting Edge: Two Distinct Motifs within the Fas Ligand Tail Regulate Fas Ligand-Mediated Costimulation J. Immunol., November 1, 2007; 179(9): 5639 - 5643. [Abstract] [Full Text] [PDF] G. Friedlein, F. El Hage, I. Vergnon, C. Richon, P. Saulnier, Y. Lecluse, A. Caignard, L. Boumsell, G. Bismuth, S. Chouaib, et al. Human CD5 Protects Circulating Tumor Antigen-Specific CTL from Tumor-Mediated Activation-Induced Cell Death J. Immunol., June 1, 2007; 178(11): 6821 - 6827. [Abstract] [Full Text] [PDF] M. Sun, K. T. Ames, I. Suzuki, and P. J. Fink The Cytoplasmic Domain of Fas Ligand Costimulates TCR Signals J. Immunol., August 1, 2006; 177(3): 1481 - 1491. [Abstract] [Full Text] [PDF]

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