ICE-proteases mediate HTLV-I tax-induced apoptotic T-cell death

K. Chlichlia, M. Busslinger, M. E. Peter, H. Walczak, P. H. Krammer, V. Schirrmacher, K. Khazaie

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

The Tax protein of Human T-cell leukemia virus type 1 (HTLV-1) is important for the T-cell immortalizing properties of this virus in vitro and is considered to be responsible for the early stages of leukemogenesis in infected hosts. Tax can upregulate expression of TNF-α and TNF-β, as well as potentiate apoptosis in activated T-cells and in serum starved murine fibroblasts. To examine the role of CD95 (APO-1/Fas) and ICE-proteases in Tax-mediated active T-cell death, Jurkat T cells expressing (APO(S)) or lacking (APO(R)) cell surface expression of CD95 (APO-1/Fas) were genetically modified to express hormone-inducible HTLV-1 Tax constructs. Hormone-inducible action of Tax alone was sufficient to promote programmed cell death in CD95-expressing Jurkat T-cell clones. In contrast, clones lacking CD95 surface expression were resistant to the antiproliferative action of Tax. Both APO(S) and APO(R) clones exhibited Tax-dependent upregulation of CD95 ligand and TNF-α. Blocking experiments suggested that while the apoptotic action of Tax critically required ICE-protease function it was largely independent of cell surface interaction of CD95 ligand or TNF-α with their corresponding receptors. These observations strongly implicate ICE-proteases in Tax-induced T-cell death, and suggest a possible involvement of CD95 in this process.

Original languageEnglish (US)
Pages (from-to)2265-2272
Number of pages8
JournalOncogene
Volume14
Issue number19
DOIs
StatePublished - Jan 1 1997

Keywords

  • APO-1
  • Apoptosis
  • CD95
  • CD95 ligand
  • ER
  • Fas
  • HTLV-I
  • ICE
  • Inducible
  • Tax

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Chlichlia, K., Busslinger, M., Peter, M. E., Walczak, H., Krammer, P. H., Schirrmacher, V., & Khazaie, K. (1997). ICE-proteases mediate HTLV-I tax-induced apoptotic T-cell death. Oncogene, 14(19), 2265-2272. https://doi.org/10.1038/sj.onc.1201070