O-GIcNAc signaling: a metabolic link between diabetes and cancer?

O-linked beta-N-acetylglucosamine (O-GIcNAc) is a sugar attachment to serine or threonine hydroxyl moieties on nuclear and cytoplasmic proteins. In many ways, O-GIcNAcylation is similar to phosphorylation because both post-translational modifications cycle rapidly in response to internal or environmental cues. O-GIcNAcylated proteins are involved in transcription, translation, cytoskeletal assembly, signal transduction, and many other cellular functions. O-GIcNAc signaling is intertwined with cellular metabolism; indeed, the donor sugar for O-GIcNAcylation (UDP-GIcNAc) is synthesized from glucose, glutamine, and UTP via the hexosamine biosynthetic pathway. Emerging research indicates that O-GIcNAc signaling and its crosstalk with phosphorylation are altered in metabolic diseases, such as diabetes and cancer.