The role of BiP in ER-associated degradation of major histocompatibility complex class I heavy chain induced by cytomegalovirus proteins

doi:10.1074/jbc.M602989200

HOME

QUICK SEARCH:

	Author:		Keyword(s):
Year:		Vol:		Page:

A more recent version of this article appeared on July 28, 2006

This Article

	Full Text (Accepted Manuscript)
	All Versions of this Article: 281/30/20910 most recent M602989200v1
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Email this article to a friend
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Request Permissions

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Hegde, N. R.
	Articles by Johnson, D. C.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Hegde, N. R.
	Articles by Johnson, D. C.

Social Bookmarking

	What's this?

Papers In Press, published online ahead of print May 25, 2006
J. Biol. Chem, 10.1074/jbc.M602989200
Submitted on March 29, 2006
Revised on May 24, 2006
Accepted on May 25, 2006

The role of BiP in ER-associated degradation of major histocompatibility complex class I heavy chain induced by cytomegalovirus proteins

Nagendra R. Hegde, Mathieu S. Chevalier, Todd W. Wisner, Michael C. Denton, Kathy Shire, Lori Frappier, and David C. Johnson

Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239-3098

Corresponding Author: johnsoda{at}ohsu.edu

Human cytomegalovirus (HCMV) US11 and US2 proteins cause rapid degradation of major histocompatibility complex (MHC) molecules, apparently by ligating cellular ER-associated degradation (ERAD) machinery. Here, we show that US11 and US2 bind the ER chaperone BiP. Four related HCMV proteins, US3, US7, US9 and US10 that do not promote degradation of MHC proteins, did not bind BiP. Silencing BiP reduced US11- and US2-mediated degradation of MHC class I heavy chain (HC) without altering the synthesis or translocation of HC into the ER or the stability of HC in the absence of US11 or US2. Induction of the unfolded protein response (UPR) did not affect US11-mediated HC degradation and could not explain the stabilization of HC when BiP was silenced. Unlike in yeast, BiP did not act by maintaining substrates in a retrotranslocation-competent form. Our studies go beyond previous observations in mammalian cells correlating BiP release with degradation, demonstrating that BiP is functionally required for US2- and US11-mediated HC degradation. Further, US2 and US11 bound BiP even when HC was absent and degradation of US2 depended on HC. These data were consistent with a model in which US2 and US11 bridge HC onto BiP promoting interactions with other ERAD proteins.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

K. Oresic and D. Tortorella
Endoplasmic reticulum chaperones participate in human cytomegalovirus US2-mediated degradation of class I major histocompatibility complex molecules
J. Gen. Virol., May 1, 2008; 89(5): 1122 - 1130.
[Abstract] [Full Text] [PDF]

V. M. Noriega and D. Tortorella
A Bipartite Trigger for Dislocation Directs the Proteasomal Degradation of an Endoplasmic Reticulum Membrane Glycoprotein
J. Biol. Chem., February 15, 2008; 283(7): 4031 - 4043.
[Abstract] [Full Text] [PDF]

B. J. Ryckman, B. L. Rainish, M. C. Chase, J. A. Borton, J. A. Nelson, M. A. Jarvis, and D. C. Johnson
Characterization of the Human Cytomegalovirus gH/gL/UL128-131 Complex That Mediates Entry into Epithelial and Endothelial Cells
J. Virol., January 1, 2008; 82(1): 60 - 70.
[Abstract] [Full Text] [PDF]

N. J. Buchkovich, T. G. Maguire, Y. Yu, A. W. Paton, J. C. Paton, and J. C. Alwine
Human Cytomegalovirus Specifically Controls the Levels of the Endoplasmic Reticulum Chaperone BiP/GRP78, Which Is Required for Virion Assembly
J. Virol., January 1, 2008; 82(1): 31 - 39.
[Abstract] [Full Text] [PDF]

S. F. de Almeida, J. V. Fleming, J. E. Azevedo, M. Carmo-Fonseca, and M. de Sousa
Stimulation of an Unfolded Protein Response Impairs MHC Class I Expression
J. Immunol., March 15, 2007; 178(6): 3612 - 3619.
[Abstract] [Full Text] [PDF]