| http://purl.uniprot.org/citations/12783888 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12783888 | http://www.w3.org/2000/01/rdf-schema#comment | "Nitric oxide (NO) may regulate gene expression by directly modifying redox state-sensitive residues of transcription factors. Here we show that the NO donor, sodium nitroprusside (SNP), rapidly represses c-myc gene transcription in a protein synthesis-independent manner in P19 embryonal carcinoma cells by inactivation of NF-kappa B. SNP treatment reduces the DNA binding ability of the constitutively active NF-kappa B heterodimer, p65/p50, and its consequent transactivation of the c-myc promoter. Repression can be blocked by the peroxynitrite scavenger, deferoxamine, but not by dithiothreitol, which triggers reduction of S-nitrosylated residues. In HEK293 cells, where tumor necrosis factor-alpha can activate NF-kappa B, SNP likewise suppresses the binding of the active NF-kappa B complex, restoring the binding of the repressive p50/p50 homodimer complex. This effect of SNP in HEK293 cells is also blocked by deferoxamine. Chromatin immunoprecipitation analysis of SNP-treated P19 cells reveals reduced association of p65, but not of p50, with the promoter region of the endogenous c-myc gene. SNP-induced p65 dissociation was associated with the recruitment of histone deacetylase 1 and 2 to the endogenous c-myc gene promoter and the subsequent deacetylation of its chromatin histone. This study is the first to demonstrate that NO modulates the transcriptional activity of the c-myc gene promoter by dissociating the active form of NF-kappa B and replacing it with a repressive NF-kappa B complex, correlated with the recruitment of gene-silencing histone deacetylases. In light of findings that NF-kappa B stimulates Myc oncoprotein expression in cancers, our findings suggest that NO should be investigated as a prospective therapeutic cancer agent."xsd:string |
| http://purl.uniprot.org/citations/12783888 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m303306200"xsd:string |
| http://purl.uniprot.org/citations/12783888 | http://purl.uniprot.org/core/author | "Park S.W."xsd:string |
| http://purl.uniprot.org/citations/12783888 | http://purl.uniprot.org/core/author | "Wei L.N."xsd:string |
| http://purl.uniprot.org/citations/12783888 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12783888 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/12783888 | http://purl.uniprot.org/core/pages | "29776-29782"xsd:string |
| http://purl.uniprot.org/citations/12783888 | http://purl.uniprot.org/core/title | "Regulation of c-myc gene by nitric oxide via inactivating NF-kappa B complex in P19 mouse embryonal carcinoma cells."xsd:string |
| http://purl.uniprot.org/citations/12783888 | http://purl.uniprot.org/core/volume | "278"xsd:string |
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