Impaired regulation of nuclear factor-kappaB 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.
Jung
M
M
Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
Zhang
Y
Y
Dimtchev
A
A
Dritschilo
A
A
D017209:Apoptosis / Q000528:radiation effects*; D001260:Ataxia Telangiectasia / Q000235:genetics; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D005720:Gamma Rays; D006801:Humans; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha