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Biochem J. 2001 Sep 1;358(Pt 2):369-77.

Ubiquitination is essential for human cytomegalovirus US11-mediated dislocation of MHC class I molecules from the endoplasmic reticulum to the cytosol.

Author information

1
Department of Medical Microbiology, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

Abstract

Human cytomegalovirus encodes two glycoproteins, US2 and US11, which cause rapid degradation of MHC class I molecules, thus preventing recognition of virus-infected cells by the immune system. This degradation process involves retrograde transport or 'dislocation' of MHC class I molecules from the endoplasmic reticulum (ER) to the cytosol, where they are deglycosylated by an N-glycanase and degraded by the proteasome. At present it is unknown whether ubiquitination is required for US2- and US11-mediated dislocation and degradation of MHC class I molecules. Here, we show that in E36ts20 hamster cells, which contain a temperature-sensitive mutation in the E1 ubiquitin-activating enzyme, US11-mediated degradation of MHC class I molecules is strongly impaired at the non-permissive temperature, indicating the necessity for ubiquitination in this process. We next addressed the question of whether ubiquitination is a condition for the retrograde movement of MHC class I molecules from the ER to the cytosol, or whether ubiquitination is merely required for recognition of dislocated MHC class I molecules by the proteasome. In the absence of a functional ubiquitin system, complexes of US11 and MHC class I molecules accumulate in the ER. In this state the membrane topology of MHC class I molecules does not significantly change, as judged from proteinase K digestions. Thus the results indicate that a functional ubiquitin system is essential for dislocation of MHC class I molecules from the ER to the cytosol.

PMID:
11513735
PMCID:
PMC1222069
DOI:
10.1042/0264-6021:3580369
[Indexed for MEDLINE]
Free PMC Article

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