Journal
JOURNAL OF MOLECULAR CELL BIOLOGY
Volume 8, Issue 1, Pages 2-16Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mjv033
Keywords
post-translational modification; O-GlcNAcylation; nuclear pore complex; protein stability; ubiquitination; nucleoporin; glycosylation
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Funding
- Discovery Grant from Natural Sciences and Engineering Research (NSERC) [RGPIN/298406-2010]
- Canadian Institutes of Health Research (CIHR) [MOP-123341]
- National Heart Lung and Blood Institute [P01HL107153]
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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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