Contribution of Lysine 11-linked Ubiquitination to MIR2-mediated Major Histocompatibility Complex Class I Internalization

The polyubiquitin chain is generated by the sequential addition of ubiquitin moieties to target molecules, a reaction between specific lysine residues that is catalyzed by E3 ubiquitin ligase. The Lys48-linked and Lys63-linked polyubiquitin chains are well established inducers of proteasome-dependen...

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Published in:The Journal of biological chemistry 2010-11, Vol.285 (46), p.35311-35319
Main Authors: Goto, Eiji, Yamanaka, Yuko, Ishikawa, Akiyo, Aoki-Kawasumi, Masami, Mito-Yoshida, Mari, Ohmura-Hoshino, Mari, Matsuki, Yohei, Kajikawa, Mizuho, Hirano, Hisashi, Ishido, Satoshi
Format: Article
Language:English
Subjects:
adaptor proteins
Adaptor Proteins, Vesicular Transport - genetics
Adaptor Proteins, Vesicular Transport - metabolism
Blotting, Western
CD8 Antigens - genetics
CD8 Antigens - metabolism
Clathrin - genetics
Clathrin - metabolism
Endocytosis
Flow Cytometry
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
HeLa Cells
Herpesvirus
Histocompatibility Antigens Class I - genetics
Histocompatibility Antigens Class I - metabolism
Humans
Lysine
Lysine - metabolism
Major histocompatibility complex
Mass Spectrometry
Mass spectroscopy
Membrane Biology
Membrane Proteins
Membrane Trafficking
MHC
Microscopy, Fluorescence
RNA Interference
Signal transduction
Ubiquitin
Ubiquitin Chain
Ubiquitin-protein ligase
Ubiquitination
Ubiquitins - genetics
Ubiquitins - metabolism
Viral Proteins - genetics
Viral Proteins - metabolism
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Summary:The polyubiquitin chain is generated by the sequential addition of ubiquitin moieties to target molecules, a reaction between specific lysine residues that is catalyzed by E3 ubiquitin ligase. The Lys48-linked and Lys63-linked polyubiquitin chains are well established inducers of proteasome-dependent degradation and signal transduction, respectively. The concept has recently emerged that polyubiquitin chain-mediated regulation is even more complex because various types of atypical polyubiquitin chains have been discovered in vivo. Here, we demonstrate that a novel complex ubiquitin chain functions as an internalization signal for major histocompatibility complex class I (MHC I) membrane proteins in vivo. Using a tetracycline-inducible expression system and quantitative mass spectrometry, we show that the polyubiquitin chain generated by the viral E3 ubiquitin ligase of Kaposi sarcoma-associated herpesvirus, MIR2, is a Lys11 and Lys63 mixed-linkage chain. This novel ubiquitin chain can function as an internalization signal for MHC I through its association with epsin1, an adaptor molecule containing ubiquitin-interacting motifs.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M110.112763