YANG LAB

Until the mid-1980s, it was widely believed that glycoproteins did not exist in the nucleus or cytoplasm. However, since Professor Gerald Hart's research team first reported this phenomenon in 1984, numerous glycoproteins have been identified in these cellular compartments, where glycosylation occurs on the hydroxyl groups (-OH) of serine or threonine via O-linked N-acetylglucosamine (O-GlcNAc). This O-GlcNAcylation (also known as O-GlcNAc glycosylation or O-GlcNAc modification) is a form of post-translational modification in which the monosaccharide GlcNAc is attached to target proteins. The monosaccharide donor, UDP-GlcNAc, is synthesized through the hexosamine biosynthetic pathway (HBP), which is linked to glucose, amino acid, fatty acid, and nucleotide metabolism. The GlcNAc moiety from UDP-GlcNAc is transferred to specific serine or threonine residues of target proteins by the enzyme O-GlcNAc transferase (OGT), while this modification on glycosylated proteins can be removed by the enzyme O-GlcNAcase (OGA). As a dynamic and reversible modification, O-GlcNAcylation is known to be involved in nearly all cellular processes, including signal transduction, transcription, translation, and protein degradation. In some cases, it can even compete with phosphorylation. To date, more than 2,000 proteins have been reported to undergo O-GlcNAcylation; however, the functional significance of this modification has been confirmed for only a small fraction (less than 10%) of these proteins. Our research laboratory focuses on elucidating the role of O-GlcNAcylation in various physiological conditions, including cancer development, metastasis, and diabetes.