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 language | English |
|---|---|
| Pages (from-to) | 6038-6041 |
| Number of pages | 4 |
| Journal | Cancer Research |
| Volume | 59 |
| Issue number | 24 |
| Publication status | Published - Dec 15 1999 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Down-regulation of nuclear factor κB is required for p53-dependent apoptosis in X-ray-irradiated mouse lymphoma cells and thymocytes
AU - Kawai, Hidehiko
AU - Yamada, Yukiko
AU - Tatsuka, Masaaki
AU - Niwa, Ohtsura
AU - Yamamoto, Ken-ichi
AU - Suzuki, Fumio
PY - 1999/12/15
Y1 - 1999/12/15
N2 - 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.
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-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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033572270&partnerID=8YFLogxK
M3 - Article
C2 - 10626786
AN - SCOPUS:0033572270
VL - 59
SP - 6038
EP - 6041
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 24
ER -