Somatic mutagenesis studies of NF-κB signaling in human T cells: Evidence for an essential role of IKKγ, in NP-κB activation by T-cell costimulatory signals and HTLV-I Tax protein

Edward W. Harhaj, LiFeng Good, Gutian Xiao, Mark Uhlik, Mary Ellen Cvijic, Isis Rivera-Walsh, Shao Cong Sun

Research output: Contribution to journalArticle

Abstract

NF-κB plays a pivotal role in normal T-cell activation and may also mediate human T-cell leukemia virus (HTLV)-induced T-cell transformation. Activation of NP-κB by both T-cell costimulatory signals and the HTLV Tax protein involves stimulation of IκB kinase (IKK). As a genetic approach to dissect the intermediate steps involved in NF-κB activation in human T cells, we performed somatic cell mutagenesis to isolate signaling defective mutant Jurkat T-cell lines. One of the mutant cell lines was shown to have a specific blockade in the IKK signaling pathway but remained competent in the c-Jun N-terminal kinase and MAP kinase pathways. Interestingly, this mutant cell line lacks expression of IKKγ, a non-catalytic component of the IKK complex. Expression of exogenous IKKγ in the mutant cells restored NF-κB activation by both the T-cell costimulation agents and Tax. These findings provide genetic evidence for the requirement of IKKγ in NF-κB signaling triggered by both T-cell costimulatory signals and HTLV-I Tax protein.

Original languageEnglish (US)
Pages (from-to)1448-1456
Number of pages9
JournalOncogene
Volume19
Issue number11
StatePublished - Mar 9 2000
Externally publishedYes

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Mutagenesis
T-Lymphocytes
Deltaretrovirus
JNK Mitogen-Activated Protein Kinases
Cell Line
tax Gene Products
Jurkat Cells
Mitogen-Activated Protein Kinase Kinases
Human T-lymphotrophic virus 1 tax protein
Phosphotransferases

Keywords

  • HTLV tax
  • IKK signaling
  • Somatic cell mutagenesis
  • T-cell costimulation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Somatic mutagenesis studies of NF-κB signaling in human T cells : Evidence for an essential role of IKKγ, in NP-κB activation by T-cell costimulatory signals and HTLV-I Tax protein. / Harhaj, Edward W.; Good, LiFeng; Xiao, Gutian; Uhlik, Mark; Cvijic, Mary Ellen; Rivera-Walsh, Isis; Sun, Shao Cong.

In: Oncogene, Vol. 19, No. 11, 09.03.2000, p. 1448-1456.

Research output: Contribution to journalArticle

Harhaj, Edward W. ; Good, LiFeng ; Xiao, Gutian ; Uhlik, Mark ; Cvijic, Mary Ellen ; Rivera-Walsh, Isis ; Sun, Shao Cong. / Somatic mutagenesis studies of NF-κB signaling in human T cells : Evidence for an essential role of IKKγ, in NP-κB activation by T-cell costimulatory signals and HTLV-I Tax protein. In: Oncogene. 2000 ; Vol. 19, No. 11. pp. 1448-1456.
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