Essential role of O-GlcNAcylation in stabilization of oncogenic factors

Abstract A reversible post-translational protein modification which involves addition of N -acetylglucosamine (GlcNAc) onto hydroxyl groups of serine and/or threonine residues which is known as O -GlcNAcylation, has emerged as a potent competitor of phosphorylation. This glycosyltransfer reaction is catalyzed by the enzyme O -linked β- N- acetylglucosamine transferase (OGT). This enzyme uses uridine diphosphate N -acetylglucosamine (UDP-GlcNAc), the end product of hexosamine biosynthetic pathway, to modify numerous nuclear and cytosolic proteins. O -GlcNAcylation influences cancer cell metabolism in such a way that hyper- O -GlcNAcylation is considered as a prominent trait of many cancers, and is proposed as a major factor enabling cancer cell proliferation and progression. Growing evidence supports a connection between O -GlcNAcylation and major oncogenic factors, including for example, c-MYC, HIF-1α, and NF-κB. A comprehensive study of the roles of O -GlcNAc modification of oncogenic factors is warranted as a thorough understanding may help drive advances in cancer diagnosis and therapy. The focus of this article is to highlight the interplay between oncogenic factors and O -GlcNAcylation along with OGT in cancer cell proliferation and survival. The prospects for OGT inhibitors will also be discussed.