Polyubiquitination is required for US11-dependent movement of MHC class I heavy chain from endoplasmic reticulum into cytosol

C. E. Shamu, D. Flierman, H. L. Ploegh, T. A. Rapoport, V. Chau

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

The human cytomegalovirus protein US11 induces the dislocation of MHC class I heavy chains from the endoplasmic reticulum (ER) into the cytosol for degradation by the proteasome. With the use of a fractionated, permeabilized cell system, we find that US11 activity is needed only in the cell membranes and that additional cytosolic factors are required for heavy chain dislocation. We identify ubiquitin as one of the required cytosolic factors. Cytosol depleted of ubiquitin does not support heavy chain dislocation from the ER, and activity can be restored by adding back purified ubiquitin. Methylated-ubiquitin or a ubiquitin mutant lacking all lysine residues does not substitute for wild-type ubiquitin, suggesting that polyubiquitination is required for US11-dependent dislocation. We propose a new function for ubiquitin in which polyubiquitination prevents the lumenal domain of the MHC class I heavy chain from moving back into the ER lumen. A similar mechanism may be operating in the dislocation of misfolded proteins from the ER in the cellular quality control pathway.

Original languageEnglish (US)
Pages (from-to)2546-2555
Number of pages10
JournalMolecular biology of the cell
Volume12
Issue number8
DOIs
StatePublished - Jan 1 2001

Fingerprint

Ubiquitin
Endoplasmic Reticulum
Cytosol
Proteasome Endopeptidase Complex
Quality Control
Lysine
Cell Membrane
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

@article{1fd5d7e4e5194950b2e962e4c4e4bb17,
title = "Polyubiquitination is required for US11-dependent movement of MHC class I heavy chain from endoplasmic reticulum into cytosol",
abstract = "The human cytomegalovirus protein US11 induces the dislocation of MHC class I heavy chains from the endoplasmic reticulum (ER) into the cytosol for degradation by the proteasome. With the use of a fractionated, permeabilized cell system, we find that US11 activity is needed only in the cell membranes and that additional cytosolic factors are required for heavy chain dislocation. We identify ubiquitin as one of the required cytosolic factors. Cytosol depleted of ubiquitin does not support heavy chain dislocation from the ER, and activity can be restored by adding back purified ubiquitin. Methylated-ubiquitin or a ubiquitin mutant lacking all lysine residues does not substitute for wild-type ubiquitin, suggesting that polyubiquitination is required for US11-dependent dislocation. We propose a new function for ubiquitin in which polyubiquitination prevents the lumenal domain of the MHC class I heavy chain from moving back into the ER lumen. A similar mechanism may be operating in the dislocation of misfolded proteins from the ER in the cellular quality control pathway.",
author = "Shamu, {C. E.} and D. Flierman and Ploegh, {H. L.} and Rapoport, {T. A.} and V. Chau",
year = "2001",
month = "1",
day = "1",
doi = "10.1091/mbc.12.8.2546",
language = "English (US)",
volume = "12",
pages = "2546--2555",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "8",

}

Polyubiquitination is required for US11-dependent movement of MHC class I heavy chain from endoplasmic reticulum into cytosol. / Shamu, C. E.; Flierman, D.; Ploegh, H. L.; Rapoport, T. A.; Chau, V.

In: Molecular biology of the cell, Vol. 12, No. 8, 01.01.2001, p. 2546-2555.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Polyubiquitination is required for US11-dependent movement of MHC class I heavy chain from endoplasmic reticulum into cytosol

AU - Shamu, C. E.

AU - Flierman, D.

AU - Ploegh, H. L.

AU - Rapoport, T. A.

AU - Chau, V.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - The human cytomegalovirus protein US11 induces the dislocation of MHC class I heavy chains from the endoplasmic reticulum (ER) into the cytosol for degradation by the proteasome. With the use of a fractionated, permeabilized cell system, we find that US11 activity is needed only in the cell membranes and that additional cytosolic factors are required for heavy chain dislocation. We identify ubiquitin as one of the required cytosolic factors. Cytosol depleted of ubiquitin does not support heavy chain dislocation from the ER, and activity can be restored by adding back purified ubiquitin. Methylated-ubiquitin or a ubiquitin mutant lacking all lysine residues does not substitute for wild-type ubiquitin, suggesting that polyubiquitination is required for US11-dependent dislocation. We propose a new function for ubiquitin in which polyubiquitination prevents the lumenal domain of the MHC class I heavy chain from moving back into the ER lumen. A similar mechanism may be operating in the dislocation of misfolded proteins from the ER in the cellular quality control pathway.

AB - The human cytomegalovirus protein US11 induces the dislocation of MHC class I heavy chains from the endoplasmic reticulum (ER) into the cytosol for degradation by the proteasome. With the use of a fractionated, permeabilized cell system, we find that US11 activity is needed only in the cell membranes and that additional cytosolic factors are required for heavy chain dislocation. We identify ubiquitin as one of the required cytosolic factors. Cytosol depleted of ubiquitin does not support heavy chain dislocation from the ER, and activity can be restored by adding back purified ubiquitin. Methylated-ubiquitin or a ubiquitin mutant lacking all lysine residues does not substitute for wild-type ubiquitin, suggesting that polyubiquitination is required for US11-dependent dislocation. We propose a new function for ubiquitin in which polyubiquitination prevents the lumenal domain of the MHC class I heavy chain from moving back into the ER lumen. A similar mechanism may be operating in the dislocation of misfolded proteins from the ER in the cellular quality control pathway.

UR - http://www.scopus.com/inward/record.url?scp=0035167960&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035167960&partnerID=8YFLogxK

U2 - 10.1091/mbc.12.8.2546

DO - 10.1091/mbc.12.8.2546

M3 - Article

C2 - 11514634

AN - SCOPUS:0035167960

VL - 12

SP - 2546

EP - 2555

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 8

ER -