Journal
JOURNAL OF CELL BIOLOGY
Volume 186, Issue 5, Pages 685-692Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200906110
Keywords
-
Categories
Funding
- Medical Research Council
- Wellcome Trust
- Newton Trust
- Cambridge Biomedical Research Centre
- MRC [G9800943, G0600823] Funding Source: UKRI
- Medical Research Council [G9800943, G0600823] Funding Source: researchfish
Ask authors/readers for more resources
The US2 and US11 gene products of human cytomegalovirus promote viral evasion by hijacking the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. US2 and US11 initiate dislocation of newly translocated major histocompatibility complex class I (MHC I) from the ER to the cytosol for proteasome-mediated degradation, thereby decreasing cell surface MHC I. Despite being instrumental in elucidating the mammalian ERAD pathway, the responsible E3 ligase or ligases remain unknown. Using a functional small interfering RNA library screen, we now identify TRC8 ( translocation in renal carcinoma, chromosome 8 gene), an ER-resident E3 ligase previously implicated as a hereditary kidney cancer gene, as required for US2-mediated MHC I ubiquitination. Depletion of TRC8 prevents MHC I ubiquitination and dislocation by US2 and restores cell surface MHC I. TRC8 forms an integral part of a novel multiprotein ER complex that contains MHC I, US2, and signal peptide peptidase. Our data show that the TRC8 E3 ligase is required for MHC I dislocation from the ER and identify a new complex associated with mammalian ERAD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available