Browsing by Subject "O-GlcNAc"

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    Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation
    (Nature Publishing Group, 2018-02-15) Sodi, Valerie L.; Bacigalupa, Zachary A.; Ferrer, Christina M.; Lee, Joyce V.; Gocal, Wiktoria A.; Mukhopadhyay, Dimpi; Wellen, Kathryn E.; Ivan, Mircea; Reginato, Mauricio J.; Medicine, School of Medicine
    Elevated O-GlcNAcylation is associated with disease states such as diabetes and cancer. O-GlcNAc transferase (OGT) is elevated in multiple cancers and inhibition of this enzyme genetically or pharmacologically inhibits oncogenesis. Here we show that O-GlcNAcylation modulates lipid metabolism in cancer cells. OGT regulates expression of the master lipid regulator the transcription factor sterol regulatory element binding protein 1 (SREBP-1) and its transcriptional targets both in cancer and lipogenic tissue. OGT regulates SREBP-1 protein expression via AMP-activated protein kinase (AMPK). SREBP-1 is critical for OGT-mediated regulation of cell survival and of lipid synthesis, as overexpression of SREBP-1 rescues lipogenic defects associated with OGT suppression, and tumor growth in vitro and in vivo. These results unravel a previously unidentified link between O-GlcNAcylation, lipid metabolism and the regulation of SREBP-1 in cancer and suggests a crucial role for O-GlcNAc signaling in transducing nutritional state to regulate lipid metabolism.