AUTHOR=Very Ninon , Vercoutter-Edouart Anne-Sophie , Lefebvre Tony , Hardivillé Stéphan , El Yazidi-Belkoura Ikram 

TITLE=Cross-Dysregulation of O-GlcNAcylation and PI3K/AKT/mTOR Axis in Human Chronic Diseases

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00602

DOI=10.3389/fendo.2018.00602

ISSN=1664-2392

ABSTRACT=<p>The hexosamine biosynthetic pathway (HBP) and the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway are considered as nutrient sensors that regulate several essential biological processes. The hexosamine biosynthetic pathway produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the substrate for <italic>O</italic>-GlcNAc transferase (OGT), the enzyme that <italic>O</italic>-GlcNAcylates proteins on serine (Ser) and threonine (Thr) residues. <italic>O</italic>-linked β-N-acetylglucosaminylation (<italic>O</italic>-GlcNAcylation) and phosphorylation are highly dynamic post-translational modifications occurring at the same or adjacent sites that regulate folding, stability, subcellular localization, partner interaction, or activity of target proteins. Here we review recent evidence of a cross-regulation of PI3K/AKT/mTOR signaling pathway and protein <italic>O</italic>-GlcNAcylation. Furthermore, we discuss their co-dysregulation in pathological conditions, e.g., cancer, type-2 diabetes (T2D), and cardiovascular, and neurodegenerative diseases.</p>