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

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...

Full description

Bibliographic Details
Published in:Frontiers in Endocrinology
Main Authors: Ninon Very, Anne-Sophie Vercoutter-Edouart, Tony Lefebvre, Stéphan Hardivillé, Ikram El Yazidi-Belkoura
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-10-01
Subjects:
O-GlcNAcylation
PI3K/AKT/mTOR
cancer
diabetes
cardiovascular
neurodegenerative diseases
Online Access:https://www.frontiersin.org/article/10.3389/fendo.2018.00602/full
Description
Summary: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 O-GlcNAc transferase (OGT), the enzyme that O-GlcNAcylates proteins on serine (Ser) and threonine (Thr) residues. O-linked β-N-acetylglucosaminylation (O-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 O-GlcNAcylation. Furthermore, we discuss their co-dysregulation in pathological conditions, e.g., cancer, type-2 diabetes (T2D), and cardiovascular, and neurodegenerative diseases.
ISSN:1664-2392

Similar Items