The nuclear factor-kappaB and p53 pathways function independently in primary cells and transformed fibroblasts responding to genotoxic damage.
With nuclear factor-kappaB (NF-kappaB) and p53 functions generally having disparate outcomes for cell survival and cell division, understanding how these pathways are coordinated following a common activation signal such as DNA damage has important implications for cancer therapy. Conflicting reports concerning NF-kappaB and p53 interplay in different cell line models prompted a reexamination of this issue using mouse primary thymocytes and embryonic fibroblasts, plus fibroblasts transformed by E1A12S. Here, we report that following the treatment of these cells with a range of stress stimuli, p53 and NF-kappaB were found to regulate cell cycling and survival independently.
Nesic
Dobrila
D
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Grumont
Raelene
R
Gerondakis
Steve
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002461:Cell Line, Transformed; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism*; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051996:Transcription Factor RelA / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000378:metabolism*
D009153:Mutagens; D016328:NF-kappa B; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin