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USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase

In the endoplasmic reticulum (ER), misfolded and unfolded proteins are eliminated by a process called ER-associated protein degradation (ERAD) in order to maintain cell homeostasis. In the ERAD pathway, several ER-localized E3 ubiquitin ligases target ERAD substrate proteins for ubiquitination and s...

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Autores principales: Harada, Kumi, Kato, Masako, Nakamura, Nobuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133830/
https://www.ncbi.nlm.nih.gov/pubmed/27827840
http://dx.doi.org/10.3390/ijms17111829
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author Harada, Kumi
Kato, Masako
Nakamura, Nobuhiro
author_facet Harada, Kumi
Kato, Masako
Nakamura, Nobuhiro
author_sort Harada, Kumi
collection PubMed
description In the endoplasmic reticulum (ER), misfolded and unfolded proteins are eliminated by a process called ER-associated protein degradation (ERAD) in order to maintain cell homeostasis. In the ERAD pathway, several ER-localized E3 ubiquitin ligases target ERAD substrate proteins for ubiquitination and subsequent proteasomal degradation. However, little is known about how the functions of the ERAD ubiquitin ligases are regulated. Recently, USP19, an ER-anchored deubiquitinating enzyme (DUB), has been suggested to be involved in the regulation of ERAD. In this study, HRD1, an ERAD ubiquitin ligase, is shown to be a novel substrate for USP19. We demonstrate that USP19 rescues HRD1 from proteasomal degradation by deubiquitination of K48-linked ubiquitin chains. In addition, the altered expression of USP19 affects the steady-state levels of HRD1. These results suggest that USP19 regulates the stability of HRD1 and provide insight into the regulatory mechanism of the ERAD ubiquitin ligases.
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spelling pubmed-51338302016-12-12 USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase Harada, Kumi Kato, Masako Nakamura, Nobuhiro Int J Mol Sci Article In the endoplasmic reticulum (ER), misfolded and unfolded proteins are eliminated by a process called ER-associated protein degradation (ERAD) in order to maintain cell homeostasis. In the ERAD pathway, several ER-localized E3 ubiquitin ligases target ERAD substrate proteins for ubiquitination and subsequent proteasomal degradation. However, little is known about how the functions of the ERAD ubiquitin ligases are regulated. Recently, USP19, an ER-anchored deubiquitinating enzyme (DUB), has been suggested to be involved in the regulation of ERAD. In this study, HRD1, an ERAD ubiquitin ligase, is shown to be a novel substrate for USP19. We demonstrate that USP19 rescues HRD1 from proteasomal degradation by deubiquitination of K48-linked ubiquitin chains. In addition, the altered expression of USP19 affects the steady-state levels of HRD1. These results suggest that USP19 regulates the stability of HRD1 and provide insight into the regulatory mechanism of the ERAD ubiquitin ligases. MDPI 2016-11-02 /pmc/articles/PMC5133830/ /pubmed/27827840 http://dx.doi.org/10.3390/ijms17111829 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Harada, Kumi
Kato, Masako
Nakamura, Nobuhiro
USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase
title USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase
title_full USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase
title_fullStr USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase
title_full_unstemmed USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase
title_short USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase
title_sort usp19-mediated deubiquitination facilitates the stabilization of hrd1 ubiquitin ligase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133830/
https://www.ncbi.nlm.nih.gov/pubmed/27827840
http://dx.doi.org/10.3390/ijms17111829
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