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Essential role of O-GlcNAcylation in stabilization of oncogenic factors

Makwana, Vivek, Ryan, Philip, Patel, Bhautikkumar, Dukie, Shailendra-Anoopkumar, Rudrawar, Santosh
Biochimica et biophysica acta 2019 v.1863 no.8 pp. 1302-1317
N-acetylglucosamine, biochemical pathways, cell proliferation, hypoxia-inducible factor 1, moieties, neoplasm cells, neoplasms, phosphorylation, post-translational modification, serine, therapeutics, threonine, transcription factor NF-kappa B, transferases, uridine diphosphate
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.