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Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import

Ubiquitin is a small polypeptide that is conjugated to proteins and commonly serves as a degradation signal. The attachment of ubiquitin (Ub) to a substrate proceeds through a multi-enzyme cascade involving an activating enzyme (E1), a conjugating enzyme (E2), and a protein ligase (E3). We previousl...

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Autores principales: Plafker, Scott M., Plafker, Kendra S., Weissman, Allan M., Macara, Ian G.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172591/
https://www.ncbi.nlm.nih.gov/pubmed/15545318
http://dx.doi.org/10.1083/jcb.200406001
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author Plafker, Scott M.
Plafker, Kendra S.
Weissman, Allan M.
Macara, Ian G.
author_facet Plafker, Scott M.
Plafker, Kendra S.
Weissman, Allan M.
Macara, Ian G.
author_sort Plafker, Scott M.
collection PubMed
description Ubiquitin is a small polypeptide that is conjugated to proteins and commonly serves as a degradation signal. The attachment of ubiquitin (Ub) to a substrate proceeds through a multi-enzyme cascade involving an activating enzyme (E1), a conjugating enzyme (E2), and a protein ligase (E3). We previously demonstrated that a murine E2, UbcM2, is imported into nuclei by the transport receptor importin-11. We now show that the import mechanism for UbcM2 and two other human class III E2s (UbcH6 and UBE2E2) uniquely requires the covalent attachment of Ub to the active site cysteine of these enzymes. This coupling of E2 activation and transport arises from the selective interaction of importin-11 with the Ub-loaded forms of these enzymes. Together, these findings reveal that Ub charging can function as a nuclear import trigger, and identify a novel link between E2 regulation and karyopherin-mediated transport.
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spelling pubmed-21725912008-03-05 Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import Plafker, Scott M. Plafker, Kendra S. Weissman, Allan M. Macara, Ian G. J Cell Biol Research Articles Ubiquitin is a small polypeptide that is conjugated to proteins and commonly serves as a degradation signal. The attachment of ubiquitin (Ub) to a substrate proceeds through a multi-enzyme cascade involving an activating enzyme (E1), a conjugating enzyme (E2), and a protein ligase (E3). We previously demonstrated that a murine E2, UbcM2, is imported into nuclei by the transport receptor importin-11. We now show that the import mechanism for UbcM2 and two other human class III E2s (UbcH6 and UBE2E2) uniquely requires the covalent attachment of Ub to the active site cysteine of these enzymes. This coupling of E2 activation and transport arises from the selective interaction of importin-11 with the Ub-loaded forms of these enzymes. Together, these findings reveal that Ub charging can function as a nuclear import trigger, and identify a novel link between E2 regulation and karyopherin-mediated transport. The Rockefeller University Press 2004-11-22 /pmc/articles/PMC2172591/ /pubmed/15545318 http://dx.doi.org/10.1083/jcb.200406001 Text en Copyright © 2004, 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
Plafker, Scott M.
Plafker, Kendra S.
Weissman, Allan M.
Macara, Ian G.
Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import
title Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import
title_full Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import
title_fullStr Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import
title_full_unstemmed Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import
title_short Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import
title_sort ubiquitin charging of human class iii ubiquitin-conjugating enzymes triggers their nuclear import
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172591/
https://www.ncbi.nlm.nih.gov/pubmed/15545318
http://dx.doi.org/10.1083/jcb.200406001
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