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Site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis

Ligand-induced endocytosis and lysosomal degradation of cognate receptors regulate the extent of cell signaling. Along with linear endocytic motifs that recruit the adaptin protein complex 2 (AP2)–clathrin molecules, monoubiquitination of receptors has emerged as a major endocytic signal. By investi...

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Autores principales: Kumar, K.G. Suresh, Barriere, Hervé, Carbone, Christopher J., Liu, Jianghuai, Swaminathan, Gayathri, Xu, Ping, Li, Ying, Baker, Darren P., Peng, Junmin, Lukacs, Gergely L., Fuchs, Serge Y.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2099190/
https://www.ncbi.nlm.nih.gov/pubmed/18056411
http://dx.doi.org/10.1083/jcb.200706034
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author Kumar, K.G. Suresh
Barriere, Hervé
Carbone, Christopher J.
Liu, Jianghuai
Swaminathan, Gayathri
Xu, Ping
Li, Ying
Baker, Darren P.
Peng, Junmin
Lukacs, Gergely L.
Fuchs, Serge Y.
author_facet Kumar, K.G. Suresh
Barriere, Hervé
Carbone, Christopher J.
Liu, Jianghuai
Swaminathan, Gayathri
Xu, Ping
Li, Ying
Baker, Darren P.
Peng, Junmin
Lukacs, Gergely L.
Fuchs, Serge Y.
author_sort Kumar, K.G. Suresh
collection PubMed
description Ligand-induced endocytosis and lysosomal degradation of cognate receptors regulate the extent of cell signaling. Along with linear endocytic motifs that recruit the adaptin protein complex 2 (AP2)–clathrin molecules, monoubiquitination of receptors has emerged as a major endocytic signal. By investigating ubiquitin-dependent lysosomal degradation of the interferon (IFN)-α/β receptor 1 (IFNAR1) subunit of the type I IFN receptor, we reveal that IFNAR1 is polyubiquitinated via both Lys48- and Lys63-linked chains. The SCF(βTrcp) (Skp1–Cullin1–F-box complex) E3 ubiquitin ligase that mediates IFNAR1 ubiquitination and degradation in cells can conjugate both types of chains in vitro. Although either polyubiquitin linkage suffices for postinternalization sorting, both types of chains are necessary but not sufficient for robust IFNAR1 turnover and internalization. These processes also depend on the proximity of ubiquitin-acceptor lysines to a linear endocytic motif and on its integrity. Furthermore, ubiquitination of IFNAR1 promotes its interaction with the AP2 adaptin complex that is required for the robust internalization of IFNAR1, implicating cooperation between site-specific ubiquitination and the linear endocytic motif in regulating this process.
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spelling pubmed-20991902008-06-03 Site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis Kumar, K.G. Suresh Barriere, Hervé Carbone, Christopher J. Liu, Jianghuai Swaminathan, Gayathri Xu, Ping Li, Ying Baker, Darren P. Peng, Junmin Lukacs, Gergely L. Fuchs, Serge Y. J Cell Biol Research Articles Ligand-induced endocytosis and lysosomal degradation of cognate receptors regulate the extent of cell signaling. Along with linear endocytic motifs that recruit the adaptin protein complex 2 (AP2)–clathrin molecules, monoubiquitination of receptors has emerged as a major endocytic signal. By investigating ubiquitin-dependent lysosomal degradation of the interferon (IFN)-α/β receptor 1 (IFNAR1) subunit of the type I IFN receptor, we reveal that IFNAR1 is polyubiquitinated via both Lys48- and Lys63-linked chains. The SCF(βTrcp) (Skp1–Cullin1–F-box complex) E3 ubiquitin ligase that mediates IFNAR1 ubiquitination and degradation in cells can conjugate both types of chains in vitro. Although either polyubiquitin linkage suffices for postinternalization sorting, both types of chains are necessary but not sufficient for robust IFNAR1 turnover and internalization. These processes also depend on the proximity of ubiquitin-acceptor lysines to a linear endocytic motif and on its integrity. Furthermore, ubiquitination of IFNAR1 promotes its interaction with the AP2 adaptin complex that is required for the robust internalization of IFNAR1, implicating cooperation between site-specific ubiquitination and the linear endocytic motif in regulating this process. The Rockefeller University Press 2007-12-03 /pmc/articles/PMC2099190/ /pubmed/18056411 http://dx.doi.org/10.1083/jcb.200706034 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
Kumar, K.G. Suresh
Barriere, Hervé
Carbone, Christopher J.
Liu, Jianghuai
Swaminathan, Gayathri
Xu, Ping
Li, Ying
Baker, Darren P.
Peng, Junmin
Lukacs, Gergely L.
Fuchs, Serge Y.
Site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis
title Site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis
title_full Site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis
title_fullStr Site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis
title_full_unstemmed Site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis
title_short Site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis
title_sort site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2099190/
https://www.ncbi.nlm.nih.gov/pubmed/18056411
http://dx.doi.org/10.1083/jcb.200706034
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