UV stimulation induces nuclear factor kappaB (NF-kappaB) DNA-binding activity but not transcriptional activation.
The cellular response to DNA-damaging agents is partly mediated by DNA-binding transcription factors such as p53 and nuclear factor kappaB (NF-kappaB). Typically NF-kappaB activation is associated with resistance to apoptosis. Following stimulation with UV light however, NF-kappaB activation has been shown to be required for programmed cell death. To study this effect further and to determine the relationship between NF-kappaB and p53 function, we have examined the effect of UV light on U2OS cells. UV stimulation resulted in the activation of NF-kappaB DNA-binding and the induction of p53. Surprisingly, and in contrast with tumour necrosis factor alpha stimulation, this UV- induced NF-kappaB was transcriptionally inert. These observations suggest a model in which the NF-kappaB switch from an anti-apoptotic to a pro-apoptotic role within the cell results from modulation of its ability to stimulate gene expression, possibly as a result of the ability of p53 to sequester transcriptional co-activator proteins such as p300/CREB (cAMP-response-element-binding protein)-binding protein.
Campbell
K J
KJ
Division of Gene Regulation and Expression, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Chapman
N R
NR
Perkins
N D
ND
D000818:Animals; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000528:radiation effects; D013997:Time Factors; D015533:Transcriptional Activation / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D016328:NF-kappa B; D004247:DNA