Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter  

作　　者：Yanping Zhu Ta-Wei Liu Zarina Madden Scott A.Yuzwa Kelsey Murray Samy Cecioni Natasha Zachara David J.Vocadlo 

机构地区：[1]Department of Chemistry,Simon Fraser University,Burnaby,British Columbia V5A 1S6,Canada [2]Department of Molecular Biology and Biochemistry,Simon Fraser University,Burnaby,British Columbia V5A 1S6,Canada [3]Department of Biological Chemistry,Johns Hopkins University Medical School,Baltimore,MD 21205,USA

出　　处：《Journal of Molecular Cell Biology》2016年第1期2-16,共15页分子细胞生物学报（英文版）

基　　金：supported by a Discovery Grant(grant no.RGPIN/298406-2010)fromthe Natural Sciences and Engineering Research(NSERC),and the Canadian Institutes of Health Research(CIHR)(grant no.MOP-123341).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.N.Z.acknowledges the support from the National Heart Lung and Blood Institute(P01HL107153).

摘　　要：O-glycosylation of the nuclear pore complex(NPC)by O-linked N-acetylglucosamine(O-GlcNAc)is conserved within metazoans.Many nucleoporins(Nups)comprising the NPC are constitutively O-GlcNAcylated,but the functional role of this modification remains enigmatic.Weshowthat loss ofO-GlcNAc,induced by either inhibition ofO-GlcNAc transferase(OGT)or deletion of the gene encoding OGT,leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups.Loss of O-GlcNAc enables increased ubiquitination of these Nups and their increased proteasomal degradation.The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells.These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter.The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans.

关 键 词：post-translational modification O-GLCNACYLATION nuclear pore complex protein stability UBIQUITINATION NUCLEOPORIN GLYCOSYLATION 

分 类 号：R73[医药卫生—肿瘤]