Impaired Regulation of Nuclear Factor-κB Results in Apoptosis Induced by Gamma Radiation

Recent studies have shown that activation of nuclear factor-kappaB (NF-kappaB) is critical for cell survival. Cells from patients with ataxia telangiectasia (AT) have an impaired NF-kappaB response to ionizing radiation. AT cells also exhibit inappropriate regulation of apoptosis. We report here that expression of a dominant negative form of IkappaB-alpha, an inhibitor of NF-kappaB, protects AT fibroblasts from apoptosis induced by gamma radiation, but it enhances apoptosis in normal fibroblasts. Furthermore, the process leading to apoptosis may involve caspase 3-mediated cleavage of IkappaB-alpha. These data suggest that regulation of NF-kappaB may play an important role in programmed cell death induced by DNA damage in AT cells.