O-linked N-acetylglucosamine(O-GlcNAc)is a dynamic post-translational modification occurring on myriad proteins in the cell nucleus,cytoplasm,and mitochondria.The donor sugar for O-Glc NAcylation,uridine-diphosphate N...O-linked N-acetylglucosamine(O-GlcNAc)is a dynamic post-translational modification occurring on myriad proteins in the cell nucleus,cytoplasm,and mitochondria.The donor sugar for O-Glc NAcylation,uridine-diphosphate N-acetylglucosamine(UDP-Glc NAc),is synthesized from glucose through the hexosamine biosynthetic pathway(HBP).The recycling of O-GlcNAc on proteins is mediated by two enzymes in cells—O-GlcNAc transferase(OGT)and O-Glc NAcase(OGA),which catalyze the addition and removal of O-GlcNAc,respectively.O-GlcNAcylation is involved in a number of important cell processes including transcription,translation,metabolism,signal transduction,and apoptosis.Deregulation of O-GlcNAcylation has been reported to be associated with various human diseases such as cancer,diabetes,neurodegenerative diseases,and cardiovascular diseases.A better understanding of the roles of O-GlcNAcylation in physiopathological processes would help to uncover novel avenues for therapeutic intervention.The aim of this review is to discuss the recent updates on the mechanisms and impacts of O-GlcNAcylation on these diseases,and its potential as a new clinical target.展开更多
基金supported by the National Natural Science Foundation of China(Nos.91753125,31270865,31322019,and 31570804)the National Key Research and Development Program of China(No.2016YFA0100303)the Zhejiang Provincial Natural Science Foundation of China(No.LR15C050001)
文摘O-linked N-acetylglucosamine(O-GlcNAc)is a dynamic post-translational modification occurring on myriad proteins in the cell nucleus,cytoplasm,and mitochondria.The donor sugar for O-Glc NAcylation,uridine-diphosphate N-acetylglucosamine(UDP-Glc NAc),is synthesized from glucose through the hexosamine biosynthetic pathway(HBP).The recycling of O-GlcNAc on proteins is mediated by two enzymes in cells—O-GlcNAc transferase(OGT)and O-Glc NAcase(OGA),which catalyze the addition and removal of O-GlcNAc,respectively.O-GlcNAcylation is involved in a number of important cell processes including transcription,translation,metabolism,signal transduction,and apoptosis.Deregulation of O-GlcNAcylation has been reported to be associated with various human diseases such as cancer,diabetes,neurodegenerative diseases,and cardiovascular diseases.A better understanding of the roles of O-GlcNAcylation in physiopathological processes would help to uncover novel avenues for therapeutic intervention.The aim of this review is to discuss the recent updates on the mechanisms and impacts of O-GlcNAcylation on these diseases,and its potential as a new clinical target.
