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Int. J. Mol. Sci. 2016, 17(11), 1829;

USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase

Department of Life Science and Technology, Tokyo Institute of Technology, 4259-B13 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Ritva Tikkanen
Received: 5 July 2016 / Revised: 26 October 2016 / Accepted: 27 October 2016 / Published: 2 November 2016
(This article belongs to the Section Biochemistry)
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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. View Full-Text
Keywords: deubiquitinating enzyme; endoplasmic reticulum; ERAD; membrane protein; ubiquitin ligase deubiquitinating enzyme; endoplasmic reticulum; ERAD; membrane protein; ubiquitin ligase

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Harada, K.; Kato, M.; Nakamura, N. USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase. Int. J. Mol. Sci. 2016, 17, 1829.

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