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| http://purl.uniprot.org/citations/12547826 | http://www.w3.org/2000/01/rdf-schema#comment | "Although epidemiological studies have long established that inorganic arsenic is a potent human carcinogen, the underlying mechanisms are still poorly understood. Recent studies suggest that inorganic arsenic may act as a tumor promoter by perturbing key signaling transduction pathways. We have shown previously that arsenite can potently activate the mitogen-activated protein kinase cascades and induce the expression of proliferation-associated genes, including proto-oncogenes c-jun and c-fos. In order to elucidate further the molecular mechanisms underlying its tumor-promoting properties, we investigated the signaling events involved in arsenite-mediated induction of c-fos and c-jun. We found that induction of both c-fos and c-jun by arsenite can be substantially inhibited by the MEK-selective inhibitor U0126, suggesting that the ERK pathway is critically involved in their up-regulation. Interestingly, arsenite dramatically induced the phosphorylation and acetylation of histone H3 preceding the induction of mRNAs encoding c-fos and c-jun. Finally, chromatin immunoprecipitation assays revealed that arsenite treatment markedly induced the phosphorylation/acetylation of histone H3 associated with the c-fos and c-jun genes through an ERK-dependent pathway. Our results strongly suggest that arsenic-triggered alterations in chromatin structure perturb specific gene transcription, including that of proto-oncogenes c-jun and c-fos, and may thereby contribute to the carcinogenic process."xsd:string |
| http://purl.uniprot.org/citations/12547826 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m300269200"xsd:string |
| http://purl.uniprot.org/citations/12547826 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/12547826 | http://purl.uniprot.org/core/author | "Li J."xsd:string |
| http://purl.uniprot.org/citations/12547826 | http://purl.uniprot.org/core/author | "Gorospe M."xsd:string |
| http://purl.uniprot.org/citations/12547826 | http://purl.uniprot.org/core/author | "Barnes J."xsd:string |
| http://purl.uniprot.org/citations/12547826 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12547826 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/12547826 | http://purl.uniprot.org/core/pages | "13183-13191"xsd:string |
| http://purl.uniprot.org/citations/12547826 | http://purl.uniprot.org/core/title | "Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts."xsd:string |
| http://purl.uniprot.org/citations/12547826 | http://purl.uniprot.org/core/volume | "278"xsd:string |
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