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, Li Feng Good, Gutian Xiao, Mark Uhlik, Mary Ellen Cvijic, Isis Rivera-Walsh, Shao Cong Sun

Research output: Contribution to journalArticle

92 Scopus citations

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
DOIs
StatePublished - Mar 9 2000

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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