{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe MYC oncogene encodes a potent transcription factor that orchestrates diverse gene‐expression programs essential for cell proliferation, cell cycle progression, DNA replication, and apoptosis. MYC directly binds to and regulates the promoters of a large repertoire of genes—including those encoding core cell cycle regulators, transcriptional machinery subunits (across RNA polymerases I, II, and III), and key microRNAs that in turn fine‐tune targets such as E2F1 and other proliferation‐ and apoptosis‐linked factors. In addition, alternative translational initiation events yield distinct MYC protein isoforms, and MYC itself directly interacts with pre‐replicative complexes to modulate replication origin activity. Collectively, these mechanisms underscore MYC’s central role as a master regulator of transcription and cell cycle control in both normal and malignant cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its transcriptional functions, MYC reprograms cellular metabolism to support the energetic and biosynthetic demands of rapid proliferation. It does so by, for example, repressing specific microRNAs to upregulate mitochondrial glutaminase—thereby stimulating glutamine catabolism—and by modulating alternative splicing events that favor the expression of the PKM2 isoform, which reinforces aerobic glycolysis. MYC also drives mitochondrial biogenesis and alters proline metabolism while collaborating with hypoxia‐responsive factors to shift the balance between oxidative phosphorylation and glycolysis. 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These observations have spurred therapeutic strategies that target MYC indirectly (via bromodomain inhibitors, spliceosome disruption, or interference with associated noncoding RNAs) as well as efforts to use MYC status as a prognostic biomarker in diverse cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kathryn A O'Donnell, Erik A Wentzel, Karen I Zeller, et al. 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