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

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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

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Thymocytes
Lymphoma
Down-Regulation
X-Rays
Apoptosis
Cyclin-Dependent Kinase Inhibitor p21
DNA
Mutant Proteins
Knockout Mice
Transcription Factors
Radiation
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Down-regulation of nuclear factor κB is required for p53-dependent apoptosis in X-ray-irradiated mouse lymphoma cells and thymocytes. / Kawai, Hidehiko; Yamada, Yukiko; Tatsuka, Masaaki; Niwa, Ohtsura; Yamamoto, Ken-ichi; Suzuki, Fumio.

In: Cancer Research, Vol. 59, No. 24, 15.12.1999, p. 6038-6041.

Research output: Contribution to journalArticle

Kawai, Hidehiko ; Yamada, Yukiko ; Tatsuka, Masaaki ; Niwa, Ohtsura ; Yamamoto, Ken-ichi ; Suzuki, Fumio. / Down-regulation of nuclear factor κB is required for p53-dependent apoptosis in X-ray-irradiated mouse lymphoma cells and thymocytes. In: Cancer Research. 1999 ; Vol. 59, No. 24. pp. 6038-6041.
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