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, Khashayarsha Khazaie

Research output: Contribution to journalArticle

47 Citations (Scopus)

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
StatePublished - 1997
Externally publishedYes

Fingerprint

Caspase 1
Human T-lymphotropic virus 1
Cell Death
T-Lymphocytes
Deltaretrovirus
Fas Ligand Protein
Jurkat Cells
Clone Cells
Up-Regulation
tax Gene Products
Hormones
Cell Communication
Fibroblasts
Apoptosis
Viruses
Serum

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

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.

ICE-proteases mediate HTLV-I tax-induced apoptotic T-cell death. / Chlichlia, K.; Busslinger, M.; Peter, M. E.; Walczak, H.; Krammer, P. H.; Schirrmacher, V.; Khazaie, Khashayarsha.

In: Oncogene, Vol. 14, No. 19, 1997, p. 2265-2272.

Research output: Contribution to journalArticle

Chlichlia, K, Busslinger, M, Peter, ME, Walczak, H, Krammer, PH, Schirrmacher, V & Khazaie, K 1997, 'ICE-proteases mediate HTLV-I tax-induced apoptotic T-cell death', Oncogene, vol. 14, no. 19, pp. 2265-2272.
Chlichlia K, Busslinger M, Peter ME, Walczak H, Krammer PH, Schirrmacher V et al. ICE-proteases mediate HTLV-I tax-induced apoptotic T-cell death. Oncogene. 1997;14(19):2265-2272.
Chlichlia, K. ; Busslinger, M. ; Peter, M. E. ; Walczak, H. ; Krammer, P. H. ; Schirrmacher, V. ; Khazaie, Khashayarsha. / ICE-proteases mediate HTLV-I tax-induced apoptotic T-cell death. In: Oncogene. 1997 ; Vol. 14, No. 19. pp. 2265-2272.
@article{9991685749254e61a68fa3d7d36c09de,
title = "ICE-proteases mediate HTLV-I tax-induced apoptotic T-cell death",
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.",
keywords = "APO-1, Apoptosis, CD95, CD95 ligand, ER, Fas, HTLV-I, ICE, Inducible, Tax",
author = "K. Chlichlia and M. Busslinger and Peter, {M. E.} and H. Walczak and Krammer, {P. H.} and V. Schirrmacher and Khashayarsha Khazaie",
year = "1997",
language = "English (US)",
volume = "14",
pages = "2265--2272",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "19",

}

TY - JOUR

T1 - ICE-proteases mediate HTLV-I tax-induced apoptotic T-cell death

AU - Chlichlia, K.

AU - Busslinger, M.

AU - Peter, M. E.

AU - Walczak, H.

AU - Krammer, P. H.

AU - Schirrmacher, V.

AU - Khazaie, Khashayarsha

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

KW - APO-1

KW - Apoptosis

KW - CD95

KW - CD95 ligand

KW - ER

KW - Fas

KW - HTLV-I

KW - ICE

KW - Inducible

KW - Tax

UR - http://www.scopus.com/inward/record.url?scp=0030913165&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030913165&partnerID=8YFLogxK

M3 - Article

VL - 14

SP - 2265

EP - 2272

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 19

ER -