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 language | English (US) |
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Pages (from-to) | 1448-1456 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 19 |
Issue number | 11 |
DOIs | |
State | Published - Mar 9 2000 |
Externally published | Yes |
Keywords
- HTLV tax
- IKK signaling
- Somatic cell mutagenesis
- T-cell costimulation
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research