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- W2895744470 abstract "1682 To identify c-Myc targets rate-limiting for proliferation of tumor cells, we stably inhibited c-Myc in several human melanoma lines via lentivirus-based shRNAs approximately to the levels detected in normal melanocytes. c-Myc depletion resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism including thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2), reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation. Individual suppression of TS, IMPDH2 or PRPS2 via specific shRNAs resulted in the decrease of dNTP pools and inhibition of proliferation of melanoma cells, thus reproducing effects caused in these cells by depletion of c-Myc. Reciprocally, concurrent overexpression of cDNAs for TS, IMPDH2 and PRPS2 in melanoma cells delayed proliferative arrest caused by inhibition of c-Myc. Overexpression of c-Myc in normal melanocytes enhanced mRNA and protein expression of the above genes and increased dNTP pools. Chromatin immunoprecipitation confirmed that TS, IMPDH2 and PRPS2 genes are direct c-Myc targets. Our data establish a direct control of dNTP metabolism by c-Myc and identify the role of such control in proliferation of tumor cells." @default.
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- W2895744470 date "2008-05-01" @default.
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- W2895744470 title "c-Myc directly regulates nucleotide metabolism" @default.
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