Ionizing radiation and UV induction of p53 protein by different pathways in ataxia-telangiectasia cells.
Cell cycle anomalies have been described in ataxia-telangiectasia cells after exposure to ionizing radiation. A recent report demonstrates that cells from these patients lack the ionizing radiation-induced increase in p53 protein seen in controls. We report here that an ionizing radiation-induced p53 response is reduced and/or delayed in cells from four ataxia-telangiectasia complementation groups. On the other hand, p53 induction is normal in all A-T complementation groups after exposure to UV-B light, an agent to which these cells are not hypersensitive. Specific inhibitors of protein kinase C and serine/threonine phosphatases prevented the radiation induction of p53 protein. Agents that produced double-strand breaks in DNA and/or inhibition of transcription caused an induction of p53 in the absence of radiation in control cells but not in ataxia-telangiectasia, but inhibitors of cell cycle progression such as mimosine and aphidicolin led to an increase in p53 in both cell types in the absence of radiation. These results suggest that there is more than one signal transduction pathway responsible for activation of p53, one of which is less efficient in ataxia-telangiectasia cells.
Khanna
K K
KK
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Brisbane, Australia.
Lavin
M F
MF
D016590:Aphidicolin / Q000494:pharmacology; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002461:Cell Line, Transformed; D004249:DNA Damage; D005786:Gene Expression Regulation / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008898:Mimosine / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics* / Q000528:radiation effects*; D014466:Ultraviolet Rays
D016159:Tumor Suppressor Protein p53; D016590:Aphidicolin; D008898:Mimosine; D011493:Protein Kinase C; D010744:Phosphoric Monoester Hydrolases