| First Author | Crawley CD | Year | 2013 |
| Journal | Nucleic Acids Res | Volume | 41 |
| Issue | 2 | Pages | 764-74 |
| PubMed ID | 23180782 | Mgi Jnum | J:200239 |
| Mgi Id | MGI:5507919 | Doi | 10.1093/nar/gks1120 |
| Citation | Crawley CD, et al. (2013) DNA damage-induced cytotoxicity is mediated by the cooperative interaction of phospho-NF-kappaB p50 and a single nucleotide in the kappaB-site. Nucleic Acids Res 41(2):764-74 |
| abstractText | Phosphorylation of the NF-kappaB subunit, p50, is necessary for cytotoxicity in response to DNA methylation damage. Here, we demonstrate that serine 329 phosphorylation regulates the interaction of p50 with specific NF-kappaB binding elements based on the identity of a single kappaB-site nucleotide. Specifically, S329 phosphorylation reduces the affinity of p50 for kappaB-sites that have a cytosine (C) at the -1 position without affecting binding to sequences with a -1 adenine. The differential interaction between phospho-p50 and the -1 base regulates the downstream transcriptional response and underlies the inhibition of anti-apoptotic gene expression following DNA damage. In genes with multiple kappaB-sites, the presence of a single -1C kappaB-site enables inhibition of NF-kappaB-dependent activity. The data suggest that interaction between phospho-p50 and the -1 kappaB nucleotide facilitates cytotoxicity in response to DNA damage. Moreover, although conservation of the entire kappaB-site sequence is not seen across species, the identity of the -1 nt in critical anti-apoptotic genes is conserved such that the overall response to DNA damage is maintained. |
