Efficient Internalization of MHC I Requires Lysine-11 and Lysine-63 Mixed Linkage Polyubiquitin Chains

Efficient Internalization of MHC I Requires Lysine-11 and Lysine-63 Mixed Linkage Polyubiquitin Chains

The downregulation of cell surface receptors by endocytosis is a fundamental requirement for the termination of signalling responses and ubiquitination is a critical regulatory step in receptor regulation. The K5 gene product of Kaposi's sarcoma-associated herpesvirus is an E3 ligase that ubiqu...

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Main Authors: Boname, Jessica M, Thomas, Mair, Stagg, Helen R, Xu, Ping, Peng, Junmin, Lehner, Paul J
Format: Online
Language:English
Published: Blackwell Publishing Ltd 2010
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551259/
id pubmed-3551259
recordtype oai_dc
spelling pubmed-35512592013-01-22 Efficient Internalization of MHC I Requires Lysine-11 and Lysine-63 Mixed Linkage Polyubiquitin Chains Boname, Jessica M Thomas, Mair Stagg, Helen R Xu, Ping Peng, Junmin Lehner, Paul J Original Articles The downregulation of cell surface receptors by endocytosis is a fundamental requirement for the termination of signalling responses and ubiquitination is a critical regulatory step in receptor regulation. The K5 gene product of Kaposi's sarcoma-associated herpesvirus is an E3 ligase that ubiquitinates and downregulates several cell surface immunoreceptors, including major histocompatibility complex (MHC) class I molecules. Here, we show that K5 targets the membrane proximal lysine of MHC I for conjugation with mixed linkage polyubiquitin chains. Quantitative mass spectrometry revealed an increase in lysine-11, as well as lysine-63, linked polyubiquitin chains on MHC I in K5-expressing cells. Using a combination of mutant ubiquitins and MHC I molecules expressing a single cytosolic lysine residue, we confirm a functional role for lysines-11 and -63 in K5-mediated MHC I endocytosis. We show that lysine-11 linkages are important for receptor endocytosis, and that complex mixed linkage polyubiquitin chains are generated in vivo. Blackwell Publishing Ltd 2010-02 2009-11-17 /pmc/articles/PMC3551259/ /pubmed/19948006 http://dx.doi.org/10.1111/j.1600-0854.2009.01011.x Text en © 2009 John Wiley & Sons A/S http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Boname, Jessica M
Thomas, Mair
Stagg, Helen R
Xu, Ping
Peng, Junmin
Lehner, Paul J
spellingShingle Boname, Jessica M
Thomas, Mair
Stagg, Helen R
Xu, Ping
Peng, Junmin
Lehner, Paul J
Efficient Internalization of MHC I Requires Lysine-11 and Lysine-63 Mixed Linkage Polyubiquitin Chains
author_facet Boname, Jessica M
Thomas, Mair
Stagg, Helen R
Xu, Ping
Peng, Junmin
Lehner, Paul J
author_sort Boname, Jessica M
title Efficient Internalization of MHC I Requires Lysine-11 and Lysine-63 Mixed Linkage Polyubiquitin Chains
title_short Efficient Internalization of MHC I Requires Lysine-11 and Lysine-63 Mixed Linkage Polyubiquitin Chains
title_full Efficient Internalization of MHC I Requires Lysine-11 and Lysine-63 Mixed Linkage Polyubiquitin Chains
title_fullStr Efficient Internalization of MHC I Requires Lysine-11 and Lysine-63 Mixed Linkage Polyubiquitin Chains
title_full_unstemmed Efficient Internalization of MHC I Requires Lysine-11 and Lysine-63 Mixed Linkage Polyubiquitin Chains
title_sort efficient internalization of mhc i requires lysine-11 and lysine-63 mixed linkage polyubiquitin chains
description The downregulation of cell surface receptors by endocytosis is a fundamental requirement for the termination of signalling responses and ubiquitination is a critical regulatory step in receptor regulation. The K5 gene product of Kaposi's sarcoma-associated herpesvirus is an E3 ligase that ubiquitinates and downregulates several cell surface immunoreceptors, including major histocompatibility complex (MHC) class I molecules. Here, we show that K5 targets the membrane proximal lysine of MHC I for conjugation with mixed linkage polyubiquitin chains. Quantitative mass spectrometry revealed an increase in lysine-11, as well as lysine-63, linked polyubiquitin chains on MHC I in K5-expressing cells. Using a combination of mutant ubiquitins and MHC I molecules expressing a single cytosolic lysine residue, we confirm a functional role for lysines-11 and -63 in K5-mediated MHC I endocytosis. We show that lysine-11 linkages are important for receptor endocytosis, and that complex mixed linkage polyubiquitin chains are generated in vivo.
publisher Blackwell Publishing Ltd
publishDate 2010
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551259/
_version_ 1611948539787608064

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