Down-regulation of nuclear factor κB is required for p53-dependent apoptosis in X-ray-irradiated mouse lymphoma cells and thymocytes

Hidehiko Kawai, Yukiko Yamada, Masaaki Tatsuka, Ohtsura Niwa, Ken Ichi Yamamoto, Fumio Suzuki

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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-dependent 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.

Original languageEnglish
Pages (from-to)6038-6041
Number of pages4
JournalCancer Research
Volume59
Issue number24
Publication statusPublished - Dec 15 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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