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Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3

The mechanism by which substrates for endoplasmic reticulum–associated degradation are retrotranslocated to the cytosol remains largely unknown, although ubiquitination is known to play a key role. The mouse γ-herpesvirus protein mK3 is a viral RING-CH–type E3 ligase that specifically targets nascen...

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Autores principales: Wang, Xiaoli, Herr, Roger A., Chua, Wei-Jen, Lybarger, Lonnie, Wiertz, Emmanuel J.H.J., Hansen, Ted H.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064207/
https://www.ncbi.nlm.nih.gov/pubmed/17502423
http://dx.doi.org/10.1083/jcb.200611063
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author Wang, Xiaoli
Herr, Roger A.
Chua, Wei-Jen
Lybarger, Lonnie
Wiertz, Emmanuel J.H.J.
Hansen, Ted H.
author_facet Wang, Xiaoli
Herr, Roger A.
Chua, Wei-Jen
Lybarger, Lonnie
Wiertz, Emmanuel J.H.J.
Hansen, Ted H.
author_sort Wang, Xiaoli
collection PubMed
description The mechanism by which substrates for endoplasmic reticulum–associated degradation are retrotranslocated to the cytosol remains largely unknown, although ubiquitination is known to play a key role. The mouse γ-herpesvirus protein mK3 is a viral RING-CH–type E3 ligase that specifically targets nascent major histocompatibility complex I heavy chain (HC) for degradation, thus blocking the immune detection of virus-infected cells. To address the question of how HC is retrotranslocated and what role mK3 ligase plays in this action, we investigated ubiquitin conjugation sites on HC using mutagenesis and biochemistry approaches. In total, our data demonstrate that mK3-mediated ubiquitination can occur via serine, threonine, or lysine residues on the HC tail, each of which is sufficient to induce the rapid degradation of HC. Given that mK3 has numerous cellular and viral homologues, it will be of considerable interest to determine the pervasiveness of this novel mechanism of ubiquitination.
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spelling pubmed-20642072007-11-29 Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3 Wang, Xiaoli Herr, Roger A. Chua, Wei-Jen Lybarger, Lonnie Wiertz, Emmanuel J.H.J. Hansen, Ted H. J Cell Biol Research Articles The mechanism by which substrates for endoplasmic reticulum–associated degradation are retrotranslocated to the cytosol remains largely unknown, although ubiquitination is known to play a key role. The mouse γ-herpesvirus protein mK3 is a viral RING-CH–type E3 ligase that specifically targets nascent major histocompatibility complex I heavy chain (HC) for degradation, thus blocking the immune detection of virus-infected cells. To address the question of how HC is retrotranslocated and what role mK3 ligase plays in this action, we investigated ubiquitin conjugation sites on HC using mutagenesis and biochemistry approaches. In total, our data demonstrate that mK3-mediated ubiquitination can occur via serine, threonine, or lysine residues on the HC tail, each of which is sufficient to induce the rapid degradation of HC. Given that mK3 has numerous cellular and viral homologues, it will be of considerable interest to determine the pervasiveness of this novel mechanism of ubiquitination. The Rockefeller University Press 2007-05-21 /pmc/articles/PMC2064207/ /pubmed/17502423 http://dx.doi.org/10.1083/jcb.200611063 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Wang, Xiaoli
Herr, Roger A.
Chua, Wei-Jen
Lybarger, Lonnie
Wiertz, Emmanuel J.H.J.
Hansen, Ted H.
Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3
title Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3
title_full Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3
title_fullStr Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3
title_full_unstemmed Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3
title_short Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3
title_sort ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce erad of mhc-i by viral e3 ligase mk3
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064207/
https://www.ncbi.nlm.nih.gov/pubmed/17502423
http://dx.doi.org/10.1083/jcb.200611063
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