| http://purl.uniprot.org/citations/27765932 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27765932 | http://www.w3.org/2000/01/rdf-schema#comment | "Many human tumors require extracellular arginine (Arg) for growth because the key enzyme for de novo biosynthesis of Arg, argininosuccinate synthetase 1 (ASS1), is silenced. These tumors are sensitive to Arg-starvation therapy using pegylated arginine deiminase (ADI-PEG20) which digests extracellular Arg. Many previous studies reported that ASS1 silencing is due to epigenetic inactivation of ASS1 expression by DNA methylation, and that the demethylation agent 5-aza-deoxycytidine (Aza-dC) can induce ASS1 expression. Moreover, it was reported that cisplatin suppresses ASS1 expression through ASS1 promoter methylation, leading to synthetic lethality to ADI-PEG20 treatment. We report here that cisplatin supppresses ASS1 expression is due to upregulation of HIF-1α and downregulation of c-Myc, which function as negative and positive regulators of ASS1 expression, respectively, by reciprocal bindings to the ASS1 promoter. In contrast, we found that Aza-dC induces ASS1 expression by downregulation of HIF-1α but upregulation of c-Myc. We further demonstrated that the clock protein DEC1 is the master regulator of HIF-1α and c-Myc that regulate ASS1. cDDP upregulates DEC1, whereas Aza-dC suppresses its expression. Using two proteasomal inhibitors bortezomib and carfilzomib which induce HIF-1α accumulation, we further demonstrated that HIF-1α is involved in ASS1 silencing for the maintenance of Arg auxotrophy for targeted Arg-starvation therapy."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.org/dc/terms/identifier | "doi:10.18632/oncotarget.12308"xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/author | "Long Y."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/author | "Chang J.T."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/author | "Chen H.H."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/author | "Kuo M.T."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/author | "Savaraj N."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/author | "Tsai W.B."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/author | "Wangpaichitr M."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/author | "Estecio M."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/author | "Feun L.G."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/name | "Oncotarget"xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/pages | "82658-82670"xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/title | "Cisplatin-induced synthetic lethality to arginine-starvation therapy by transcriptional suppression of ASS1 is regulated by DEC1, HIF-1alpha, and c-Myc transcription network and is independent of ASS1 promoter DNA methylation."xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/27765932 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27765932 |
| http://purl.uniprot.org/citations/27765932 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27765932 |
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| http://purl.uniprot.org/uniprot/#_A0A0S2Z3D8-mappedCitation-27765932 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27765932 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z3F1-mappedCitation-27765932 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27765932 |
| http://purl.uniprot.org/uniprot/#_A0N2G3-mappedCitation-27765932 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27765932 |