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O‐GlcNAc occurs cotranslationally to stabilize nascent polypeptides
Author(s) -
Vocadlo David,
Zhu Yanping,
Liu TaWei,
Cecioni Samy,
Eskandari Raieh,
Zandberg Wesley,
Willems Lianne
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.378.3
Subject(s) - glycosylation , ribosome , biology , proteostasis , microbiology and biotechnology , biochemistry , chemistry , gene , rna
Nucleocytoplasmic glycosylation of proteins with O‐linked N‐acetylglucosamine residues (O‐GlcNAc) is mediated by the glycosyltransferase O‐GlcNAc transferase (OGT). O‐GlcNAc is recognized as a common post‐translational modification and is found on hundreds of proteins within all metazoans studied to date. O‐GlcNAc has emerged as a regulator of diverse cellular processes ranging from gene expression through to circadian rhythm. Notably, impairments in cellular O‐GlcNAcylation have been found to lead to decreases in the levels of various proteins and this is one mechanism by which O‐GlcNAc seems to exert its varied physiological effects. Here we use a chemical biology approach in combination with biochemical fractionation to show that O‐GlcNAcylation also occurs on polypeptides that are emerging from the ribosome. Using both chemical and genetic blockade of OGT we show that this cotranslational O‐GlcNAcylation protects nascent polypeptide chains from premature degradation by decreasing their 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. We describe our recent findings and discuss the similarities between cotranslational O‐GlcNAcylation and the roles played by cotranslational N‐glycosylation occurring within the secretory pathway. Support or Funding Information Financial support through a Discovery Grant (Grant number: RGPIN/298406‐2010) the Natural Sciences and Engineering Research (NSERC) and the Canadian Institutes of Health Research (CIHR) (Grant number: MOP‐102756) is gratefully acknowledged. Y.Z. thanks the CIHR for support through a postdoctoral fellowship. D.J.V. acknowledges the kind support of the Canada Research Chairs program for a Tier I Canada Research Chair in Chemical Glycobiology and NSERC for support as an E.W.R. Steacie Memorial Fellow.