Open AccessRole of O-linked N-acetylglucosamine protein modification in cellular (patho)physiology
Author(s) -
John C. Chatham,
Jianhua Zhang,
Adam R. Wende
Publication year - 2021
Publication title -
physiological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 13.853
H-Index - 342
eISSN - 1522-1210
pISSN - 0031-9333
DOI - 10.1152/physrev.00043.2019
Subject(s) - endoplasmic reticulum , glycosylation , golgi apparatus , threonine , microbiology and biotechnology , serine , biology , n acetylglucosamine , phosphorylation , chromatin , chromatin remodeling , cytoplasm , biochemistry , enzyme , gene
In the mid-1980s, the identification of serine and threonine residues on nuclear and cytoplasmic proteins modified by a N -acetylglucosamine moiety ( O -GlcNAc) via an O -linkage overturned the widely held assumption that glycosylation only occurred in the endoplasmic reticulum, Golgi apparatus, and secretory pathways. In contrast to traditional glycosylation, the O -GlcNAc modification does not lead to complex, branched glycan structures and is rapidly cycled on and off proteins by O -GlcNAc transferase (OGT) and O -GlcNAcase (OGA), respectively. Since its discovery, O -GlcNAcylation has been shown to contribute to numerous cellular functions, including signaling, protein localization and stability, transcription, chromatin remodeling, mitochondrial function, and cell survival. Dysregulation in O -GlcNAc cycling has been implicated in the progression of a wide range of diseases, such as diabetes, diabetic complications, cancer, cardiovascular, and neurodegenerative diseases. This review will outline our current understanding of the processes involved in regulating O -GlcNAc turnover, the role of O -GlcNAcylation in regulating cellular physiology, and how dysregulation in O -GlcNAc cycling contributes to pathophysiological processes.