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

Hewitt, Eric W., Duncan, Lidia, Mufti, Dina, Baker, John, Stevenson, Philip G. and Lehner, Paul J. (2002) Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation. EMBO Journal, 21 10: 2418-2429. doi:10.1093/emboj/21.10.2418


Author Hewitt, Eric W.
Duncan, Lidia
Mufti, Dina
Baker, John
Stevenson, Philip G.
Lehner, Paul J.
Title Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation
Journal name EMBO Journal   Check publisher's open access policy
ISSN 0261-4189
1460-2075
Publication date 2002-05-15
Year available 2002
Sub-type Article (original research)
DOI 10.1093/emboj/21.10.2418
Open Access Status Not yet assessed
Volume 21
Issue 10
Start page 2418
End page 2429
Total pages 12
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract 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.
Keyword HHV8 K3
MHC class I
TSG101
Ubiquitin
Viral evasion
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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