Open AccessO‐Glc NA cylation: a bridge between glucose and cell differentiation
Author(s) -
Sun Chao,
Shang Jin,
Yao Yuan,
Yin Xiaohong,
Liu Minghan,
Liu Huan,
Zhou Yue
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12807
Subject(s) - cellular differentiation , microbiology and biotechnology , adipogenesis , extracellular , intracellular , biology , protein kinase a , cell fate determination , signal transduction , cell , cell growth , kinase , transcription factor , biochemistry , chemistry , mesenchymal stem cell , gene
Glucose is the major energy supply and a critical metabolite for most cells and is especially important when cell is differentiating. High or low concentrations of glucose enhances or inhibits the osteogenic, chondrogenic and adipogenic differentiation of cell via the insulin, transforming growth factor‐β and peroxisome proliferator‐activated receptor γ pathways, among others. New evidence implicates the hexosamine biosynthetic pathway as a mediator of crosstalk between glucose flux, cellular signalling and epigenetic regulation of cell differentiation. Extracellular glucose flux alters intracellular O‐Glc NA cylation levels through the hexosamine biosynthetic pathway. Signalling molecules that are important for cell differentiation, including protein kinase C , extracellular signal‐regulated kinase, Runx2, CCAAT /enhancer‐binding proteins, are modified by O‐Glc NA cylation. Thus, O‐Glc NA cylation markedly alters cell fate during differentiation via the post‐transcriptional modification of proteins. Furthermore, O‐Glc NA cylation and phosphorylation show complex interactions during cell differentiation: they can either non‐competitively occupy different sites on a substrate or competitively occupy a single site or proximal sites. Therefore, the influence of glucose on cell differentiation via O‐Glc NA cylation offers a potential target for controlling tissue homoeostasis and regeneration in ageing and disease. Here, we review recent progress establishing an emerging relationship among glucose concentration, O‐Glc NA cylation levels and cell differentiation.