O-linked N-acetylglucosaminyltransferase (OGT) (OGT)

O-linked N-acetylglucosaminyltransferase (OGT) is the unique enzyme responsible for the post-translational modification of nuclear, cytoplasmic, and mitochondrial proteins with a single N-acetylglucosamine (O-GlcNAc) moiety (UniProt O15294). This modification, known as O-GlcNAcylation, serves as a key nutrient sensor, linking cellular metabolism—specifically the hexosamine biosynthetic pathway—to signaling and gene expression (PubMed: 23303720). OGT regulates thousands of proteins involved in diverse processes such as the cell cycle, transcription, and proteasomal degradation. Dysregulation of OGT and aberrant O-GlcNAcylation levels are strongly linked to the pathogenesis of cancer, where it promotes tumor growth and metastasis, as well as metabolic disorders like insulin resistance and neurodegenerative diseases like Alzheimer's (PubMed: 30104658). Consequently, OGT has emerged as a significant therapeutic target, with various small-molecule inhibitors like OSMI-1 currently under investigation to modulate its activity in disease states (PubMed: 25531960). However, the essential nature of OGT for cell survival poses a significant challenge for the development of safe and effective clinical therapies.

Other names

O-GlcNAc transferaseUDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferaseOGTO-linked N-acetylglucosamine transferase 110 kDa subunit

Inhibition of the catalytic activity of O-linked N-acetylglucosaminyltransferase to prevent the addition of O-GlcNAc moieties to substrate proteins, thereby modulating downstream signaling and metabolic pathways.