Glycosylation of the Nuclear Pore

The O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) posttranslational modification was first discovered 30 years ago and is highly concentrated in the nuclear pore. In the years since the discovery of this single sugar modification, substantial progress has been made in understanding the biochemistry of O‐GlcNAc and its regulation. Nonetheless, O‐GlcNAc modification of proteins continues to be overlooked, due in large part to the lack of reliable methods available for its detection. Recently, a new crop of immunological and chemical detection reagents has changed the research landscape. Using these tools, approximately 1000 O‐GlcNAc‐modified proteins have been identified. While other forms of glycosylation are typically associated with extracellular proteins, O‐GlcNAc is abundant on nuclear and cytoplasmic proteins. In particular, phenylalanine–glycine nucleoporins are heavily O‐GlcNAc‐modified. Recent experiments are beginning to provide insight into the functional implications of O‐GlcNAc modification on certain proteins, but its role in the nuclear pore has remained enigmatic. However, tantalizing new results suggest that O‐GlcNAc may play roles in regulating nucleocytoplasmic transport.