NF-κB-inducing kinase and IκB kinase participate in human T-cell leukemia virus I tax-mediated NF-κB activation

Mark Uhlik, Li Feng Good, Gutian Xiao, Edward W. Harhaj, Ebrahim Zandi, Michael Karin, Shao Cong Sun

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

The tax gene product of human T-cell leukemia virus I induces aberrant expression of various cellular genes, which contributes to transformation of host cells. Induction of many Tax target genes is mediated through transcription factor NF-κB. Here we show that Tax triggers activation of cellular protein kinases, IκB kinase α (IKKα) and IKKβ, which phosphorylate the NF-κB inhibitory protein IκBα, resulting in its degradation and NF-κB activation. Constitutive IKK activation occurs in both Tax-transfected and human T-cell leukemia virus I-infected T cells. We further demonstrate that Tax-mediated NF-κB signaling also requires the NF- κB-inducing kinase (NIK). Consistently, inactive forms of either IKKs or NIK attenuate Tax-mediated NF-κB activation. Therefore, Tax activates NF-κB by targeting cellular signaling molecules, including both IKKs and NIK.

Original languageEnglish (US)
Pages (from-to)21132-21136
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number33
DOIs
StatePublished - Aug 14 1998

Fingerprint

Human T-lymphotropic virus 1
T-cells
Taxation
Viruses
Phosphotransferases
Chemical activation
pX Genes
Genes
Protein Kinases
Cell signaling
Transcription Factors
T-Lymphocytes
Degradation
Molecules
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Uhlik, Mark ; Good, Li Feng ; Xiao, Gutian ; Harhaj, Edward W. ; Zandi, Ebrahim ; Karin, Michael ; Sun, Shao Cong. / NF-κB-inducing kinase and IκB kinase participate in human T-cell leukemia virus I tax-mediated NF-κB activation. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 33. pp. 21132-21136.
@article{e310a074288d45b48608f80e79ace2bf,
title = "NF-κB-inducing kinase and IκB kinase participate in human T-cell leukemia virus I tax-mediated NF-κB activation",
abstract = "The tax gene product of human T-cell leukemia virus I induces aberrant expression of various cellular genes, which contributes to transformation of host cells. Induction of many Tax target genes is mediated through transcription factor NF-κB. Here we show that Tax triggers activation of cellular protein kinases, IκB kinase α (IKKα) and IKKβ, which phosphorylate the NF-κB inhibitory protein IκBα, resulting in its degradation and NF-κB activation. Constitutive IKK activation occurs in both Tax-transfected and human T-cell leukemia virus I-infected T cells. We further demonstrate that Tax-mediated NF-κB signaling also requires the NF- κB-inducing kinase (NIK). Consistently, inactive forms of either IKKs or NIK attenuate Tax-mediated NF-κB activation. Therefore, Tax activates NF-κB by targeting cellular signaling molecules, including both IKKs and NIK.",
author = "Mark Uhlik and Good, {Li Feng} and Gutian Xiao and Harhaj, {Edward W.} and Ebrahim Zandi and Michael Karin and Sun, {Shao Cong}",
year = "1998",
month = "8",
day = "14",
doi = "10.1074/jbc.273.33.21132",
language = "English (US)",
volume = "273",
pages = "21132--21136",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "33",

}

NF-κB-inducing kinase and IκB kinase participate in human T-cell leukemia virus I tax-mediated NF-κB activation. / Uhlik, Mark; Good, Li Feng; Xiao, Gutian; Harhaj, Edward W.; Zandi, Ebrahim; Karin, Michael; Sun, Shao Cong.

In: Journal of Biological Chemistry, Vol. 273, No. 33, 14.08.1998, p. 21132-21136.

Research output: Contribution to journalArticle

TY - JOUR

T1 - NF-κB-inducing kinase and IκB kinase participate in human T-cell leukemia virus I tax-mediated NF-κB activation

AU - Uhlik, Mark

AU - Good, Li Feng

AU - Xiao, Gutian

AU - Harhaj, Edward W.

AU - Zandi, Ebrahim

AU - Karin, Michael

AU - Sun, Shao Cong

PY - 1998/8/14

Y1 - 1998/8/14

N2 - The tax gene product of human T-cell leukemia virus I induces aberrant expression of various cellular genes, which contributes to transformation of host cells. Induction of many Tax target genes is mediated through transcription factor NF-κB. Here we show that Tax triggers activation of cellular protein kinases, IκB kinase α (IKKα) and IKKβ, which phosphorylate the NF-κB inhibitory protein IκBα, resulting in its degradation and NF-κB activation. Constitutive IKK activation occurs in both Tax-transfected and human T-cell leukemia virus I-infected T cells. We further demonstrate that Tax-mediated NF-κB signaling also requires the NF- κB-inducing kinase (NIK). Consistently, inactive forms of either IKKs or NIK attenuate Tax-mediated NF-κB activation. Therefore, Tax activates NF-κB by targeting cellular signaling molecules, including both IKKs and NIK.

AB - The tax gene product of human T-cell leukemia virus I induces aberrant expression of various cellular genes, which contributes to transformation of host cells. Induction of many Tax target genes is mediated through transcription factor NF-κB. Here we show that Tax triggers activation of cellular protein kinases, IκB kinase α (IKKα) and IKKβ, which phosphorylate the NF-κB inhibitory protein IκBα, resulting in its degradation and NF-κB activation. Constitutive IKK activation occurs in both Tax-transfected and human T-cell leukemia virus I-infected T cells. We further demonstrate that Tax-mediated NF-κB signaling also requires the NF- κB-inducing kinase (NIK). Consistently, inactive forms of either IKKs or NIK attenuate Tax-mediated NF-κB activation. Therefore, Tax activates NF-κB by targeting cellular signaling molecules, including both IKKs and NIK.

UR - http://www.scopus.com/inward/record.url?scp=0032516520&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032516520&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.33.21132

DO - 10.1074/jbc.273.33.21132

M3 - Article

C2 - 9694868

AN - SCOPUS:0032516520

VL - 273

SP - 21132

EP - 21136

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 33

ER -