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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Main Authors:	Harada, Kumi, Kato, Masako, Nakamura, Nobuhiro
Format:	Online
Language:	English
Published:	MDPI 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133830/

id	pubmed-5133830
recordtype	oai_dc
spelling	pubmed-51338302016-12-12 USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase Harada, Kumi Kato, Masako Nakamura, Nobuhiro 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/).
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	Harada, Kumi Kato, Masako Nakamura, Nobuhiro
spellingShingle	Harada, Kumi Kato, Masako Nakamura, Nobuhiro USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase
author_facet	Harada, Kumi Kato, Masako Nakamura, Nobuhiro
author_sort	Harada, Kumi
title	USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase
title_short	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_sort	usp19-mediated deubiquitination facilitates the stabilization of hrd1 ubiquitin ligase
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.
publisher	MDPI
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133830/
_version_	1613753027471081472

USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase

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