A novel function of VCP (valosin-containing protein; p97) in the control of N-glycosylation of proteins in the endoplasmic reticulum.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lass, A; McConnell, E; Nowis, D; Mechref, Y; Kang, P; Novotny, MV; Wójcik, C

Published Date

  • June 1, 2007

Published In

Volume / Issue

  • 462 / 1

Start / End Page

  • 62 - 73

PubMed ID

  • 17493577

International Standard Serial Number (ISSN)

  • 0003-9861

Digital Object Identifier (DOI)

  • 10.1016/j.abb.2007.04.010

Language

  • eng

Conference Location

  • United States