![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 12, Issue 8, 2546-2555, August 2001
§ and
*Department of Cell Biology, Harvard Medical School, Boston,
Massachusetts 02115; 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.
Department of Pathology, Harvard
Medical School, Boston, Massachusetts 02115; Howard
Hughes Medical Institute, Harvard Medical School, Department of Cell
Biology, Boston, Massachusetts 02115; and Department of
Cellular and Molecular Physiology, Pennsylvania State University
College of Medicine, Hershey, Pennsylvania 17033
This article has been cited by other articles:
|
|
 |
|
  H. R. Stagg, M. Thomas, D. van den Boomen, E. J.H.J. Wiertz, H. A. Drabkin, R. M. Gemmill, and P. J. Lehner The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER J. Cell Biol., September 7, 2009; 186(5): 685 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Oresic, C. L. Ng, and D. Tortorella TRAM1 Participates in Human Cytomegalovirus US2- and US11-mediated Dislocation of an Endoplasmic Reticulum Membrane Glycoprotein J. Biol. Chem., February 27, 2009; 284(9): 5905 - 5914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, L. Li, and Y. Ye Inhibition of p97-dependent Protein Degradation by Eeyarestatin I J. Biol. Chem., March 21, 2008; 283(12): 7445 - 7454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Baker and D. Tortorella Dislocation of an Endoplasmic Reticulum Membrane Glycoprotein Involves the Formation of Partially Dislocated Ubiquitinated Polypeptides J. Biol. Chem., September 14, 2007; 282(37): 26845 - 26856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. P. Pearce, Y. Wang, G. G. Kelley, and R. J. H. Wojcikiewicz SPFH2 Mediates the Endoplasmic Reticulum-associated Degradation of Inositol 1,4,5-Trisphosphate Receptors and Other Substrates in Mammalian Cells J. Biol. Chem., July 13, 2007; 282(28): 20104 - 20115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Hassink, M. T. Barel, S. B. Van Voorden, M. Kikkert, and E. J. Wiertz Ubiquitination of MHC Class I Heavy Chains Is Essential for Dislocation by Human Cytomegalovirus-encoded US2 but Not US11 J. Biol. Chem., October 6, 2006; 281(40): 30063 - 30071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Flierman, C. S. Coleman, C. M. Pickart, T. A. Rapoport, and V. Chau E2-25K mediates US11-triggered retro-translocation of MHC class I heavy chains in a permeabilized cell system PNAS, August 1, 2006; 103(31): 11589 - 11594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Hegde, M. S. Chevalier, T. W. Wisner, M. C. Denton, K. Shire, L. Frappier, and D. C. Johnson The Role of BiP in Endoplasmic Reticulum-associated Degradation of Major Histocompatibility Complex Class I Heavy Chain Induced by Cytomegalovirus Proteins J. Biol. Chem., July 28, 2006; 281(30): 20910 - 20919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Oresic, V. Noriega, L. Andrews, and D. Tortorella A Structural Determinant of Human Cytomegalovirus US2 Dictates the Down-regulation of Class I Major Histocompatibility Molecules J. Biol. Chem., July 14, 2006; 281(28): 19395 - 19406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Utama, Y. H. Shen, B. M. Mitchell, I. T. Makagiansar, Y. Gan, R. Muthuswamy, S. Duraisamy, D. Martin, X. Wang, M.-X. Zhang, et al. Mechanisms for human cytomegalovirus-induced cytoplasmic p53 sequestration in endothelial cells J. Cell Sci., June 15, 2006; 119(12): 2457 - 2467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, Y. Ye, W. Lencer, and T. H. Hansen The Viral E3 Ubiquitin Ligase mK3 Uses the Derlin/p97 Endoplasmic Reticulum-associated Degradation Pathway to Mediate Down-regulation of Major Histocompatibility Complex Class I Proteins J. Biol. Chem., March 31, 2006; 281(13): 8636 - 8644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Barel, N. Pizzato, P. Le Bouteiller, E. J. H. J. Wiertz, and F. Lenfant Subtle sequence variation among MHC class I locus products greatly influences sensitivity to HCMV US2- and US11-mediated degradation Int. Immunol., January 1, 2006; 18(1): 173 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Lilley and H. L. Ploegh Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane PNAS, October 4, 2005; 102(40): 14296 - 14301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Katiyar, S. Joshi, and W. J. Lennarz The Retrotranslocation Protein Derlin-1 Binds Peptide:N-Glycanase to the Endoplasmic Reticulum Mol. Biol. Cell, October 1, 2005; 16(10): 4584 - 4594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Gong, D. R. Keeney, M. Molinari, and Z. Zhou Degradation of Trafficking-defective Long QT Syndrome Type II Mutant Channels by the Ubiquitin-Proteasome Pathway J. Biol. Chem., May 13, 2005; 280(19): 19419 - 19425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Spear and D. T.W. Ng Single, context-specific glycans can target misfolded glycoproteins for ER-associated degradation J. Cell Biol., April 11, 2005; 169(1): 73 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, R. Connors, M. R. Harris, T. H. Hansen, and L. Lybarger Requirements for the Selective Degradation of Endoplasmic Reticulum-Resident Major Histocompatibility Complex Class I Proteins by the Viral Immune Evasion Molecule mK3 J. Virol., April 1, 2005; 79(7): 4099 - 4108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Doolman, G. S. Leichner, R. Avner, and J. Roitelman Ubiquitin Is Conjugated by Membrane Ubiquitin Ligase to Three Sites, including the N Terminus, in Transmembrane Region of Mammalian 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase: IMPLICATIONS FOR STEROL-REGULATED ENZYME DEGRADATION J. Biol. Chem., September 10, 2004; 279(37): 38184 - 38193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-L. Song and R. A. DeBose-Boyd Ubiquitination of 3-Hydroxy-3-methylglutaryl-CoA Reductase in Permeabilized Cells Mediated by Cytosolic E1 and a Putative Membrane-bound Ubiquitin Ligase J. Biol. Chem., July 2, 2004; 279(27): 28798 - 28806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Fiebiger, C. Hirsch, J. M. Vyas, E. Gordon, H. L. Ploegh, and D. Tortorella Dissection of the Dislocation Pathway for Type I Membrane Proteins with a New Small Molecule Inhibitor, Eeyarestatin Mol. Biol. Cell, April 1, 2004; 15(4): 1635 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kikkert, R. Doolman, M. Dai, R. Avner, G. Hassink, S. van Voorden, S. Thanedar, J. Roitelman, V. Chau, and E. Wiertz Human HRD1 Is an E3 Ubiquitin Ligase Involved in Degradation of Proteins from the Endoplasmic Reticulum J. Biol. Chem., January 30, 2004; 279(5): 3525 - 3534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Flierman, Y. Ye, M. Dai, V. Chau, and T. A. Rapoport Polyubiquitin Serves as a Recognition Signal, Rather than a Ratcheting Molecule, during Retrotranslocation of Proteins across the Endoplasmic Reticulum Membrane J. Biol. Chem., September 12, 2003; 278(37): 34774 - 34782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Furman, J. Loureiro, H. L. Ploegh, and D. Tortorella Ubiquitinylation of the Cytosolic Domain of a Type I Membrane Protein Is Not Required to Initiate Its Dislocation from the Endoplasmic Reticulum J. Biol. Chem., September 12, 2003; 278(37): 34804 - 34811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Lilley, D. Tortorella, and H. L. Ploegh Dislocation of a Type I Membrane Protein Requires Interactions between Membrane-spanning Segments within the Lipid Bilayer Mol. Biol. Cell, September 1, 2003; 14(9): 3690 - 3698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ye, H. H. Meyer, and T. A. Rapoport Function of the p97-Ufd1-Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains J. Cell Biol., July 7, 2003; 162(1): 71 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Palmer, K. B. Kruse, S. W. Fewell, S. M. Buchanan, J. L. Brodsky, and A. A. McCracken Differential requirements of novel A1PiZ degradation deficient (ADD) genes in ER-associated protein degradation J. Cell Sci., June 1, 2003; 116(11): 2361 - 2373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Chevalier and D. C. Johnson Human Cytomegalovirus US3 Chimeras Containing US2 Cytosolic Residues Acquire Major Histocompatibility Class I and II Protein Degradation Properties J. Virol., April 15, 2003; 77(8): 4731 - 4738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Chevalier, G. M. Daniels, and D. C. Johnson Binding of Human Cytomegalovirus US2 to Major Histocompatibility Complex Class I and II Proteins Is Not Sufficient for Their Degradation J. Virol., August 15, 2002; 76(16): 8265 - 8275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rabinovich, A. Kerem, K.-U. Frohlich, N. Diamant, and S. Bar-Nun AAA-ATPase p97/Cdc48p, a Cytosolic Chaperone Required for Endoplasmic Reticulum-Associated Protein Degradation Mol. Cell. Biol., January 15, 2002; 22(2): 626 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Furman, H. L. Ploegh, and D. Tortorella Membrane-specific, Host-derived Factors Are Required for US2- and US11-mediated Degradation of Major Histocompatibility Complex Class I Molecules J. Biol. Chem., January 25, 2002; 277(5): 3258 - 3267. [Abstract] [Full Text] [PDF]
|
|
