Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation

The Kaposi's sarcoma‐associated herpes virus gene product K3 (KK3) subverts the MHC class I antigen presentation pathway by downregulating MHC class I from the plasma membrane. We now show that KK3 associates with MHC class I molecules and promotes ubiquitylation of class I after export from th...

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Bibliographic Details
Published in:The EMBO journal 2002-05, Vol.21 (10), p.2418-2429
Main Authors: Hewitt, Eric W., Duncan, Lidia, Mufti, Dina, Baker, John, Stevenson, Philip G., Lehner, Paul J.
Format: Article
Language:English
Subjects:
AK3 protein
DNA-Binding Proteins - metabolism
EMBO23
EMBO31
Endosomal Sorting Complexes Required for Transport
endosome
HeLa Cells
HHV8 K3
Histocompatibility Antigens Class I - metabolism
Humans
K3 protein
Kaposi's sarcoma-associated herpesvirus
Leucine Zippers
MHC class I
Open Reading Frames
Protein Transport
Recombinant Proteins - metabolism
Sarcoma
Transcription Factors - metabolism
Transfection
TSG101
TSG101 protein
ubiquitin
Ubiquitin - metabolism
ubiquitylation
viral evasion
Viral Proteins - metabolism
Zinc Fingers
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Summary:The Kaposi's sarcoma‐associated herpes virus gene product K3 (KK3) subverts the MHC class I antigen presentation pathway by downregulating MHC class I from the plasma membrane. We now show that KK3 associates with MHC class I molecules and promotes ubiquitylation of class I after export from the endoplasmic reticulum. Ubiquitylation requires the KK3 N‐terminal plant homeodomain and provides the signal for class I internalization at the plasma membrane. Once internalized, ubiquitylated MHC class I is targeted to the late endocytic pathway, where it is degraded. Depletion by small interfering RNA of TSG101, a ubiquitin enzyme 2 variant protein involved in late endosomal sorting, prevents class I degradation and preserves cell surface class I expression in KK3‐expressing cells. These results suggest a mechanism by which the KK3‐induced class I ubiquitylation provides a signal for both internalization and sorting to the late endosomal pathway for degradation. KK3 is the first viral gene product that subverts the trafficking of a host protein via the ubiquitin‐dependent endosomal sorting machinery.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/21.10.2418