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

Agnieszka Lass, Elizabeth McConnell, Dominika Nowis, Yehia Mechref, Pilsoo Kang, Milos V. Novotny, Cezary Wojcik

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

α-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 αTCR despite inducing accumulation of α1-antitrypsin, another ERAD substrate. Furthermore, while depletion of VCP does not affect levels of α1-antitrypsin, it induces an increase in levels of αTCR. RNAi of VCP induces preferential accumulation of αTCR 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.

Original languageEnglish (US)
Pages (from-to)62-73
Number of pages12
JournalArchives of Biochemistry and Biophysics
Volume462
Issue number1
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

Fingerprint

Glycosylation
T-Cell Antigen Receptor
Endoplasmic Reticulum
Mannose
Proteins
Degradation
Polysaccharides
Glycoproteins
Proteasome Endopeptidase Complex
Substrates
RNA Interference
CDC48 protein

Keywords

  • Derlin
  • ER-associated degradation (ERAD)
  • Proteasome
  • Protein degradation
  • Retrotranslocation
  • T-cell receptor
  • Ubiquitin
  • Valosin-containing protein (VCP)

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

A novel function of VCP (valosin-containing protein; p97) in the control of N-glycosylation of proteins in the endoplasmic reticulum. / Lass, Agnieszka; McConnell, Elizabeth; Nowis, Dominika; Mechref, Yehia; Kang, Pilsoo; Novotny, Milos V.; Wojcik, Cezary.

In: Archives of Biochemistry and Biophysics, Vol. 462, No. 1, 01.06.2007, p. 62-73.

Research output: Contribution to journalArticle

Lass, Agnieszka ; McConnell, Elizabeth ; Nowis, Dominika ; Mechref, Yehia ; Kang, Pilsoo ; Novotny, Milos V. ; Wojcik, Cezary. / A novel function of VCP (valosin-containing protein; p97) in the control of N-glycosylation of proteins in the endoplasmic reticulum. In: Archives of Biochemistry and Biophysics. 2007 ; Vol. 462, No. 1. pp. 62-73.
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