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

Oncogene volume 19, pages 1448–1456 (2000)Cite this article

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 NF-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.

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Acknowledgements

We greatly acknowledge Drs B Seed and I Verma and The Fred Hutchinson Cancer Research Center for reagents. This study was supported by Public Health Service grants 1 R01 CA68471.

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Author notes

  1. Edward W Harhaj and LiFeng Good: EW Harhaj and LF Good contributed equally to this paper

Authors and Affiliations

  1. Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, 17033, Pennsylvania, PA, USA

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

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Harhaj, E., Good, L., Xiao, G. et al. Somatic mutagenesis studies of NF-κB signaling in human T cells: evidence for an essential role of IKKγ in NF-κB activation by T-cell costimulatory signals and HTLV-I Tax protein. Oncogene 19, 1448–1456 (2000). https://doi.org/10.1038/sj.onc.1203445

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