Essential role of O-GlcNAcylation in stabilization of oncogenic factors

• Published in: Biochimica et biophysica acta. General subjects Vol. 1863; no. 8; pp. 1302 - 1317
• Main Authors: Makwana, Vivek, Ryan, Philip, Patel, Bhautikkumar, Dukie, Shailendra-Anoopkumar, Rudrawar, Santosh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2019
• Subjects: Acetylglucosamine - metabolism; beta Catenin - metabolism; biochemical pathways; cell proliferation; Enzyme Inhibitors - metabolism; Glycosylation; Humans; hypoxia-inducible factor 1; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; moieties; N-acetylglucosamine; neoplasm cells; neoplasms; Neoplasms - metabolism; O-GlcNAcylation; OGT enzyme; OGT inhibitors; Oncogenes; Oncogenic factors; phosphorylation; post-translational modification; serine; Sterol Regulatory Element Binding Proteins - metabolism; therapeutics; threonine; transcription factor NF-kappa B; transferases; uridine diphosphate; O-GlcNAcylation; OGT enzyme; Oncogenic factors; OGT inhibitors
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2019.04.002

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. •Aberrant O-GlcNAcylation is considered as hallmark of cancer.•Hyper O-GlcNAcylation favours stabilization of oncogenic factors.•Transcription of oncogenic factors lead to uncontrolled cell division, invasion and metastasis of cancer cells.•Development of a potent, selective and cell permeable inhibitors of OGT enzyme is required.