| http://purl.uniprot.org/citations/18677108 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18677108 | http://www.w3.org/2000/01/rdf-schema#comment | "To identify C-MYC targets rate-limiting for proliferation of malignant melanoma, we stably inhibited C-MYC in several human metastatic melanoma lines via lentivirus-based shRNAs approximately to the levels detected in normal melanocytes. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation. shRNA-mediated suppression of TS, IMPDH2 or PRPS2 resulted in the decrease of dNTP pools and retardation of the cell cycle progression of melanoma cells in a manner similar to that of C-MYC-depletion in those cells. Reciprocally, concurrent overexpression of cDNAs for TS, IMPDH2 and PRPS2 delayed proliferative arrest caused by inhibition of C-MYC in melanoma cells. Overexpression of C-MYC in normal melanocytes enhanced expression of the above enzymes and increased individual dNTP pools. Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. Moreover, all three proteins express at higher levels in cells from several metastatic melanoma lines compared to normal melanocytes. Our data establish a novel functional link between C-MYC and dNTP metabolism and identify its role in proliferation of tumor cells."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.org/dc/terms/identifier | "doi:10.4161/cc.6390"xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/author | "Mathews C.K."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/author | "Shewach D.S."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/author | "Zhuang D."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/author | "Im M."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/author | "Nikiforov M.A."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/author | "Wheeler L.J."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/author | "Grachtchouk V."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/author | "Mannava S."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/author | "Slavina E.G."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/name | "Cell Cycle"xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/pages | "2392-2400"xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/title | "Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells."xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/18677108 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18677108 |
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