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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3933-3939. Prepublished online as a Blood First Edition Paper on January 10, 2006; DOI 10.1182/blood-2005-06-2567. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-06-2567v1 107/10/3933    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 Krueger, A. Articles by Li-Weber, M. Search for Related Content PubMed PubMed Citation Articles by Krueger, A. Articles by Li-Weber, M. Related Collections Immunobiology Apoptosis Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY HTLV-1 Tax protects against CD95-mediated apoptosis by induction of the cellular FLICE-inhibitory protein (c-FLIP) Andreas Krueger, Stefanie C. Fas, Marco Giaisi, Marc Bleumink, Anette Merling, Christine Stumpf, Sven Baumann, Denise Holtkotte, Valerie Bosch, Peter H. Krammer, and Min Li-Weber From the Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany; and Research Program Infection and Cancer, German Cancer Research Center, Heidelberg, Germany. The HTLV-1 transactivator protein Tax is essential for malignant transformation of CD4 T cells, ultimately leading to adult T-cell leukemia/lymphoma (ATL). Malignant transformation may involve development of apoptosis resistance. In this study we investigated the molecular mechanisms by which HTLV-1 Tax confers resistance toward CD95-mediated apoptosis. We show that Tax-expressing T-cell lines derived from HTLV-1–infected patients express elevated levels of c-FLIPL and c-FLIPS. The levels of c-FLIP correlated with resistance toward CD95-mediated apoptosis. Using an inducible system we demonstrated that both resistance toward CD95-mediated apoptosis and induction of c-FLIP are dependent on Tax. In addition, analysis of early cleavage of the BH3-only Bcl-2 family member Bid, a direct caspase-8 substrate, revealed that apoptosis is inhibited at a CD95 death receptor proximal level in Tax-expressing cells. Finally, using siRNA we directly showed that c-FLIP confers Tax-mediated resistance toward CD95-mediated apoptosis. In conclusion, our data suggest an important mechanism by which expression of HTLV-1 Tax may lead to immune escape of infected T cells and, thus, to persistent infection and transformation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Chan, E. R. Bivins-Smith, M. S. Smith, and A. D. Yurochko Transcriptome Analysis of NF-{kappa}B- and Phosphatidylinositol 3-Kinase-Regulated Genes in Human Cytomegalovirus-Infected Monocytes J. Virol., January 15, 2008; 82(2): 1040 - 1046. [Abstract] [Full Text] [PDF] A. Troeger, I. Schmitz, M. Siepermann, L. Glouchkova, U. Gerdemann, G. E. Janka-Schaub, K. Schulze-Osthoff, and D. Dilloo Up-regulation of c-FLIPS+R upon CD40 stimulation is associated with inhibition of CD95-induced apoptosis in primary precursor B-ALL Blood, July 1, 2007; 110(1): 384 - 387. [Abstract] [Full Text] [PDF] U. Testa and R. Riccioni Deregulation of apoptosis in acute myeloid leukemia Haematologica, January 1, 2007; 92(1): 81 - 94. [Abstract] [Full Text] [PDF] S.-H. Chiou, Y.-P. Yang, J.-C. Lin, C.-H. Hsu, H.-C. Jhang, Y.-T. Yang, C.-H. Lee, L. L. T. Ho, W.-M. Hsu, H.-H. Ku, et al. The Immediate Early 2 Protein of Human Cytomegalovirus (HCMV) Mediates the Apoptotic Control in HCMV Retinitis through Up-Regulation of the Cellular FLICE-Inhibitory Protein Expression J. Immunol., November 1, 2006; 177(9): 6199 - 6206. [Abstract] [Full Text] [PDF]

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