PT  - JOURNAL ARTICLE
AU  - Kawai, Hidehiko
AU  - Yamada, Yukiko
AU  - Tatsuka, Masaaki
AU  - Niwa, Ohtsura
AU  - Yamamoto, Ken-ichi
AU  - Suzuki, Fumio
TI  - Down-Regulation of Nuclear Factor κB Is Required for p53-dependent Apoptosis in X-Ray-irradiated Mouse Lymphoma Cells and Thymocytes
DP  - 1999 Dec 15
TA  - Cancer Research
PG  - 6038--6041
VI  - 59
IP  - 24
4099  - http://cancerres.aacrjournals.org/content/59/24/6038.short
4100  - http://cancerres.aacrjournals.org/content/59/24/6038.full
SO  - Cancer Res1999 Dec 15; 59
AB  - Transcription factors p53 and nuclear factor κB (NF-κB) have been implicated in apoptosis induced by DNA-damaging agents, but the relationship between these two factors at the molecular level is largely unknown. We have isolated apoptosis-resistant mutant sublines from a radiosensitive mouse lymphoma 3SB cell line that undergoes p53-depen-dent apoptosis after X-ray irradiation, and we have analyzed the NF-κB activity. Two of these apoptosis-resistant sublines expressed mutant p53 protein and exhibited a defect in the induction of cyclin-dependent kinase inhibitor p21 after X-ray irradiation. A decrease in the DNA binding activity of NF-κB was observed in the parental 3SB cells after exposure to X-rays, whereas the same activity was unaffected by radiation in the two mutant sublines. A similar down-regulation of NF-κB activity by X-rays was observed in thymocytes derived from p53 wild-type and heterozygous mice, but not in thymocytes from p53 homozygous knockout mice. These results suggest that NF-κB inactivation is p53 dependent and is required for X-ray-induced apoptosis in thymic lymphoma cells and normal thymocytes.