UV-mediated NF-kappaB activation is abolished in deficient XPC/D primary fibroblasts.
Genetic pathologies involving deficits in DNA repair, like xeroderma pigmentosum (XP), show recurrent cell death, tissue degeneration and oncogenesis due to high sensitivity to ultraviolet radiation (UV). Various inducers including UV activate NF-kappaB, a pathway largely involved in cell proliferation and apoptosis. However, the mechanism(s) involving NF-kappaB activation by UV are poorly understood. To improve this knowledge, we examined NF-kappaB in two XP cell groups (XPC and XPD/TTD). XPC/D primary fibroblasts possess functional NF-kappaB dimers, and pro-inflammatory cytokines consistently activate NF-kappaB pathway. Contrarily, UV-mediated NF-kappaB activation is practically absent, whereas kappaB-specific DNA binding and transcriptional activity are dramatically undermined. These results indicate that lack of UV responsiveness at the NF-kappaB level is a common feature of XPC/D cells, suggesting that XP proteins might act upstream on NF-kappaB activity induced by UV. These observations help us to better understand the UV sensitivity and compromised survival of XP deficient cells.
Muotri
Alysson R
AR
The Salk Institute for Biological Studies, La Jolla, California, USA.
Bottero
Virginie
V
Tergaonkar
Vinay
V
Correa
Ricardo G
RG
D017209:Apoptosis; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014466:Ultraviolet Rays; D051759:Xeroderma Pigmentosum Group D Protein / Q000172:deficiency* / Q000235:genetics
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; C086984:XPC protein, human; D004247:DNA; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human