TY - JOUR
T1 - A novel function of VCP (valosin-containing protein; p97) in the control of N-glycosylation of proteins in the endoplasmic reticulum
AU - Lass, Agnieszka
AU - McConnell, Elizabeth
AU - Nowis, Dominika
AU - Mechref, Yehia
AU - Kang, Pilsoo
AU - Novotny, Milos V.
AU - Wójcik, Cezary
N1 - Funding Information:
This work was supported by the Biomedical Research Grant from Indiana University School of Medicine 22-812-57 (C.W.), by the American Cancer Society Grant IRG-84-002-22 (C.W.), and by the NIH/NCRR Grant RR018942 as the National Center for Glycomics and Glycoproteomics (M.V.N. and Y.M.). We are highly appreciative of a fellowship from Merck Research Laboratories to one of us (P.K.). D.N. was on leave from the Department of Immunology, Center of Biostructure Research, Medical University of Warsaw, Poland. We acknowledge the generous gifts of pCDNA3.1-HA-α-TCR from Dr. Ron Kopito (Stanford University) and of pCMV-α1-antitrypsin Hong Kong from Dr. Nobuko Hosokawa (Kyoto University, Kyoto, Japan).
PY - 2007/6/1
Y1 - 2007/6/1
N2 - 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.
AB - 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.
KW - Derlin
KW - ER-associated degradation (ERAD)
KW - Proteasome
KW - Protein degradation
KW - Retrotranslocation
KW - T-cell receptor
KW - Ubiquitin
KW - Valosin-containing protein (VCP)
UR - http://www.scopus.com/inward/record.url?scp=34248561455&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2007.04.010
DO - 10.1016/j.abb.2007.04.010
M3 - Article
C2 - 17493577
AN - SCOPUS:34248561455
SN - 0003-9861
VL - 462
SP - 62
EP - 73
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1
ER -