O-GlcNAc cycling: implications for neurodegenerative disorders.
The dynamic post-translational modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc), termed O-GlcNAcylation, is an important mechanism for modulating cellular signaling pathways. O-GlcNAcylation impacts transcription, translation, organelle trafficking, proteasomal degradation and apoptosis. O-GlcNAcylation has been implicated in the etiology of several human diseases including type-2 diabetes and neurodegeneration. This review describes the pair of enzymes responsible for the cycling of this post-translational modification: O-GlcNAc transferase (OGT) and beta-N-acetylglucosaminidase (OGA), with a focus on the function of their structural domains. We will also highlight the important processes and substrates regulated by these enzymes, with an emphasis on the role of O-GlcNAc as a nutrient sensor impacting insulin signaling and the cellular stress response. Finally, we will focus attention on the many ways by which O-GlcNAc cycling may affect the cellular machinery in the neuroendocrine and central nervous systems.
Laboratory of Cell Biology and Biochemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Brooke D
BD
Lazarus
Dona C
DC
Love
John A
JA
Hanover
D000117:Acetylglucosamine / Q000378:metabolism*; D000118:Acetylglucosaminidase / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D000118:Acetylglucosaminidase; D000117:Acetylglucosamine