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J. Mol. Cell Biol. 2016, 8(1): 2-16, DOI: 10.1093/jmcb/mjv033
Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter
Yanping Zhu1,2, Ta-Wei Liu1,2, Zarina Madden1, Scott A. Yuzwa2, Kelsey Murray2, Samy Cecioni1, Natasha Zachara3, and David J. Vocadlo1,2,*
1Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada
2Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada
3Department of Biological Chemistry, Johns Hopkins University Medical School, Baltimore, MD 21205, USA
post-translational modification, O-GlcNAcylation, nuclear pore complex, protein stability, ubiquitination, nucleoporin, glycosylation
*Correspondence to
David J. Vocadlo, E-mail: dvocadlo@sfu.ca

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. We show that loss of O-GlcNAc, induced by either inhibition of O-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.

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