title: O-GlcNAc occurs cotranslationally to stabilize nascent polypeptide chains.
abstract: Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is recognized as a conserved post-translational modification found in all metazoans. O-GlcNAc has been proposed to regulate diverse cellular processes. Impaired cellular O-GlcNAcylation has been found to lead to decreases in the levels of various proteins, which is one mechanism by which O-GlcNAc seems to exert its varied physiological effects. Here we show that O-GlcNAcylation also occurs cotranslationally. This process protects nascent polypeptide chains from premature degradation by decreasing cotranslational ubiquitylation. Given that hundreds of proteins are O-GlcNAcylated within cells, our findings suggest that cotranslational O-GlcNAcylation may be a phenomenon regulating proteostasis of an array of nucleocytoplasmic proteins. These findings set the stage to assess whether O-GlcNAcylation has a role in protein quality control in a manner that bears similarity with the role played by N-glycosylation within the secretory pathway.
authors.affiliation: 1] Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada. [2] Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada..
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: 1] Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada. [2] Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada..
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada..
authors.forename: Samy
authors.initials: S
authors.lastname: Cecioni
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada..
authors.forename: Razieh
authors.initials: R
authors.lastname: Eskandari
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada..
authors.forename: Wesley F
authors.initials: WF
authors.lastname: Zandberg
authors.affiliation: 1] Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada. [2] Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada..
authors.forename: David J
authors.identifier: 0000000168975558
authors.initials: DJ
authors.lastname: Vocadlo
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry*; D000818:Animals; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids; D011499:Protein Processing, Post-Translational; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000737:chemistry; D054875:Ubiquitination
chemical_list: D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; D000117:Acetylglucosamine