Requirement of the human T-cell leukemia virus (HTLV-1) tax-stimulated HIAP-1 gene for the survival of transformed lymphocytes.

Published

Journal Article

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-kappaB (NF-kappaB) 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-kappaB activation.

Full Text

Duke Authors

Cited Authors

  • Wäldele, K; Silbermann, K; Schneider, G; Ruckes, T; Cullen, BR; Grassmann, R

Published Date

  • June 1, 2006

Published In

Volume / Issue

  • 107 / 11

Start / End Page

  • 4491 - 4499

PubMed ID

  • 16467195

Pubmed Central ID

  • 16467195

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2005-08-3138

Language

  • eng

Conference Location

  • United States