Ubiquitination is essential for human cytomegalovirus US11-mediated dislocation of MHC class I molecules from the endoplasmic reticulum to the cytosol
In: Biochemical Journal, Jg. 358 (2001-08-24), S. 369-377
Online
unknown
Zugriff:
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.
Titel: |
Ubiquitination is essential for human cytomegalovirus US11-mediated dislocation of MHC class I molecules from the endoplasmic reticulum to the cytosol
|
---|---|
Autor/in / Beteiligte Person: | Marjolein, KIKKERT ; Gerco, HASSINK ; Martine, BAREL ; Christian, HIRSCH ; Fimme Jan van der, WAL ; Emmanuel, WIERTZ |
Link: | |
Zeitschrift: | Biochemical Journal, Jg. 358 (2001-08-24), S. 369-377 |
Veröffentlichung: | Portland Press Ltd., 2001 |
Medientyp: | unknown |
ISSN: | 1470-8728 (print) ; 0264-6021 (print) |
DOI: | 10.1042/bj3580369 |
Schlagwort: |
|
Sonstiges: |
|