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 language | English (US) |
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Pages (from-to) | 2265-2272 |
Number of pages | 8 |
Journal | Oncogene |
Volume | 14 |
Issue number | 19 |
DOIs | |
State | Published - 1997 |
Keywords
- APO-1
- Apoptosis
- CD95
- CD95 ligand
- ER
- Fas
- HTLV-I
- ICE
- Inducible
- Tax
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research