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, 19 (11), 1448-56

Somatic Mutagenesis Studies of NF-kappa B Signaling in Human T Cells: Evidence for an Essential Role of IKK Gamma in NF-kappa B Activation by T-cell Costimulatory Signals and HTLV-I Tax Protein

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Somatic Mutagenesis Studies of NF-kappa B Signaling in Human T Cells: Evidence for an Essential Role of IKK Gamma in NF-kappa B Activation by T-cell Costimulatory Signals and HTLV-I Tax Protein

E W Harhaj et al. Oncogene.

Abstract

NF-kappa B 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 NF-kappa B by both T-cell costimulatory signals and the HTLV Tax protein involves stimulation of I kappa B kinase (IKK). As a genetic approach to dissect the intermediate steps involved in NF-kappa B 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 IKK gamma, a non-catalytic component of the IKK complex. Expression of exogenous IKK gamma in the mutant cells restored NF-kappa B activation by both the T-cell costimulation agents and Tax. These findings provide genetic evidence for the requirement of IKK gamma in NF-kappa B signaling triggered by both T-cell costimulatory signals and HTLV-I Tax protein.

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