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Related Collections Apoptosis Signal Transduction Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2001, Vol. 98, No. 13, pp. 3860-3863 BRIEF REPORT The antitumor ether lipid ET-18-OCH3 induces apoptosis through translocation and capping of Fas/CD95 into membrane rafts in human leukemic cells Consuelo Gajate and Faustino Mollinedo From the Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain, and Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Spain. The antitumor ether lipid ET-18-OCH3 promotes apoptosis in tumor cells through intracellular activation of Fas/CD95. Results of this study showed that ET-18-OCH3 induces cocapping of Fas and membrane rafts, specialized plasma membrane regions involved in signaling, before the onset of apoptosis in human leukemic cells. Patches of membrane rafts accumulated Fas clusters in leukemic cells treated with ET-18-OCH3. Sucrose gradient centrifugation of Triton X-100 cell lysates showed that Fas translocated into membrane rafts following ET-18-OCH3 treatment of T-leukemic Jurkat cells. Disruption of membrane raft integrity by methyl--cyclodextrin or filipin inhibited ET-18-OCH3-induced apoptosis in leukemic primary cells and cell lines. Fas clustering was also inhibited by methyl--cyclodextrin. These data indicate that ET-18-OCH3 reorganizes membrane rafts to trigger apoptosis in human leukemic cells, and that Fas coaggregation with membrane rafts is required for ET-18-OCH3-induced apoptosis. This translocation of Fas into membrane rafts may provide a mechanism for amplifying Fas signaling by reorganization of membrane microdomains. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Petrovas, B. Chaon, D. R. Ambrozak, D. A. Price, J. J. Melenhorst, B. J. Hill, C. Geldmacher, J. P. Casazza, P. K. Chattopadhyay, M. Roederer, et al. Differential Association of Programmed Death-1 and CD57 with Ex Vivo Survival of CD8+ T Cells in HIV Infection J. Immunol., July 15, 2009; 183(2): 1120 - 1132. [Abstract] [Full Text] [PDF] F. Mollinedo, C. Gajate, A. I. Morales, E. del Canto-Janez, N. Justies, F. Collia, J. V. Rivas, M. Modolell, and A. Iglesias Novel Anti-Inflammatory Action of Edelfosine Lacking Toxicity with Protective Effect in Experimental Colitis J. Pharmacol. Exp. Ther., May 1, 2009; 329(2): 439 - 449. [Abstract] [Full Text] [PDF] A. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020