title: A novel function of VCP (valosin-containing protein; p97) in the control of N-glycosylation of proteins in the endoplasmic reticulum.
abstract: alpha-Chain of T-cell receptor (TCR) is a typical ERAD (ER-associated degradation) substrate degraded in the absence of other TCR subunits. Depletion of derlin 1 fails to induce accumulation of alphaTCR despite inducing accumulation of alpha1-antitrypsin, another ERAD substrate. Furthermore, while depletion of VCP does not affect levels of alpha1-antitrypsin, it induces an increase in levels of alphaTCR. RNAi of VCP induces preferential accumulation of alphaTCR with less mannose residues, suggesting its retention within the ER. Mass spectrometric analysis of cellular N-linked glycans revealed that depletion of VCP decreases the level of high-mannose glycoproteins, increases the levels of truncated low-mannose glycoproteins and induces changes in the abundance of complex glycans assembled in post-ER compartments. Since proteasome inhibition was unable to mimic those changes, they cannot be regarded as a simple consequence of inhibited ERAD but represent a complex effect of VCP on the function of the ER.
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine-Evansville, Evansville, IN 47712, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lass
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McConnell
authors.forename: Dominika
authors.initials: D
authors.lastname: Nowis
authors.forename: Yehia
authors.initials: Y
authors.lastname: Mechref
authors.forename: Pilsoo
authors.initials: P
authors.lastname: Kang
authors.forename: Milos V
authors.initials: MV
authors.lastname: Novotny
authors.forename: Cezary
authors.initials: C
authors.lastname: Wójcik
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry; D006031:Glycosylation; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008358:Mannose / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D014176:Protein Biosynthesis; D021381:Protein Transport; D034622:RNA Interference; D025801:Ubiquitin / Q000737:chemistry; D000074405:Valosin Containing Protein; D000515:alpha 1-Antitrypsin / Q000737:chemistry
chemical_list: D018797:Cell Cycle Proteins; C487709:DERL1 protein, human; D006023:Glycoproteins; D008565:Membrane Proteins; D025801:Ubiquitin; D000515:alpha 1-Antitrypsin; D049452:Green Fluorescent Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; D008358:Mannose