SEARCH:   Advanced

Blood, 1 June 2006, Vol. 107, No. 11, pp. 4491-4499. Prepublished online as a Blood First Edition Paper on February 7, 2006; DOI 10.1182/blood-2005-08-3138. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3138v1 107/11/4491    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 Wäldele, K. Articles by Grassmann, R. Search for Related Content PubMed PubMed Citation Articles by Wäldele, K. Articles by Grassmann, R. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Requirement of the human T-cell leukemia virus (HTLV-1) tax-stimulated HIAP-1 gene for the survival of transformed lymphocytes Katja Wäldele, Katrin Silbermann, Grit Schneider, Tobias Ruckes, Bryan R. Cullen, and Ralph Grassmann From the Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Erlangen, Germany; and the Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC. Human T cell leukemia virus type 1 (HTLV-1), the cause of adult T cell leukemia (ATL), induces clonal expansion of infected T-cells in nonleukemic individuals and immortalizes T cells in vitro. The resistance against apoptotic stimuli of these cells hints at a viral survival function in addition to a proliferation-stimulating activity. Here we describe the up-regulation of the antiapoptotic HIAP-1/CIAP-2 gene as a consistent phenotype of HTLV-1–transformed and ATL-derived cultures and its stimulation by the viral oncoprotein Tax. Cotransfections revealed a 60-fold increase of HIAP-1 promoter activity mediated by Tax mainly via nuclear factor-B (NF-B) activation. To address the relevance of virally increased HIAP-1 levels for the survival of HTLV-1–transformed cells, its expression was RNA interference (RNAi) suppressed using a lentiviral transduction system. This resulted in a dramatic reduction of cell growth, a strong induction of apoptosis rates, and increased caspases 3/7 activity, which is known to be suppressed by HIAP-1. Thus, the Tax-mediated HIAP-1 overexpression is required to suppress endogenous apoptosis and, therefore, is essential for the survival of HTLV-1–transformed lymphocytes. Moreover, this points to HIAP-1 as an important target of the HTLV-1–mediated NF-B activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Liu, S. Enomoto, C. A. Lancto, M. S. Abrahamsen, and M. S. Rutherford Inhibition of Apoptosis in Cryptosporidium parvum-Infected Intestinal Epithelial Cells Is Dependent on Survivin Infect. Immun., August 1, 2008; 76(8): 3784 - 3792. [Abstract] [Full Text] [PDF] K. Pichler, T. Kattan, J. Gentzsch, A. K. Kress, G. P. Taylor, C. R. M. Bangham, and R. Grassmann Strong induction of 4-1BB, a growth and survival promoting costimulatory receptor, in HTLV-1-infected cultured and patients' T cells by the viral Tax oncoprotein Blood, May 1, 2008; 111(9): 4741 - 4751. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020