H. Kawai et al., Down-regulation of nuclear factor kappa B is required for p53-dependent apoptosis in X-ray-irradiated mouse lymphoma cells and thymocytes, CANCER RES, 59(24), 1999, pp. 6038-6041
Transcription factors p53 and nuclear factor kappa B (NF-kappa B) have been
implicated in apoptosis induced by DNA-damaging agents, but the relationsh
ip between these two factors at the molecular level is largely unknown, We
have isolated apoptosis-resistant mutant sublines from a radiosensitive mou
se lymphoma 3SB cell line that undergoes p53-dependent apoptosis after X-ra
y irradiation, and we have analyzed the NF-kappa B activity, Two of these a
poptosis-resistant sublines expressed mutant p53 protein and exhibited a de
fect in the induction of cyclin-dependent kinase inhibitor p21 after X-ray
irradiation, A decrease in the DNA binding activity of NF-kappa B was obser
ved in the parental 3SB cells after exposure to X-rays, whereas the same ac
tivity was unaffected by radiation in the two mutant sublines. A similar do
wn-regulation of NF-kappa B activity by X-rays was observed in thymocytes d
erived from p53 wild-type and heterozygous mice, but not in thymocytes from
p53 homozygous knockout mice. These results suggest that NF-kappa B inacti
vation is p53 dependent and is required for X-ray-induced apoptosis in thym
ic lymphoma cells and normal thymocytes.