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Correction published on 25 April 2017, see Int. J. Mol. Sci. 2017, 18(5), 902.

Open AccessReview
Int. J. Mol. Sci. 2017, 18(3), 483; doi:10.3390/ijms18030483

The Regulations of Deubiquitinase USP15 and Its Pathophysiological Mechanisms in Diseases

1
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan
3
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117, Singapore
4
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 807, Taiwan
5
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6
Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
7
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
8
Translational Research Center, Cancer Center and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
9
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Nobuhiro Nakamura
Received: 9 January 2017 / Revised: 14 February 2017 / Accepted: 18 February 2017 / Published: 24 February 2017
(This article belongs to the Special Issue Ubiquitin System)
View Full-Text   |   Download PDF [1734 KB, uploaded 26 April 2017]   |  

Abstract

Deubiquitinases (DUBs) play a critical role in ubiquitin-directed signaling by catalytically removing the ubiquitin from substrate proteins. Ubiquitin-specific protease 15 (USP15), a member of the largest subfamily of cysteine protease DUBs, contains two conservative cysteine (Cys) and histidine (His) boxes. USP15 harbors two zinc-binding motifs that are essential for recognition of poly-ubiquitin chains. USP15 is grouped into the same category with USP4 and USP11 due to high degree of homology in an N-terminal region consisting of domains present in ubiquitin-specific proteases (DUSP) domain and ubiquitin-like (UBL) domain. USP15 cooperates with COP9 signalosome complex (CSN) to maintain the stability of cullin-ring ligase (CRL) adaptor proteins by removing the conjugated ubiquitin chains from RBX1 subunit of CRL. USP15 is also implicated in the stabilization of the human papillomavirus type 16 E6 oncoprotein, adenomatous polyposis coli, and IκBα. Recently, reports have suggested that USP15 acts as a key regulator of TGF-β receptor-signaling pathways by deubiquitinating the TGF-β receptor itself and its downstream transducers receptor-regulated SMADs (R-SMADs), including SMAD1, SMAD2, and SMAD3, thus activating the TGF-β target genes. Although the importance of USP15 in pathologic processes remains ambiguous so far, in this review, we endeavor to summarize the literature regarding the relationship of the deubiquitinating action of USP15 with the proteins involved in the regulation of Parkinson’s disease, virus infection, and cancer-related signaling networks. View Full-Text
Keywords: deubiquitinase; ubiquitin-specific protease 15; TGF-β; IκBα; cancer-related signaling networks; Parkinson’s disease deubiquitinase; ubiquitin-specific protease 15; TGF-β; IκBα; cancer-related signaling networks; Parkinson’s disease
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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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MDPI and ACS Style

Chou, C.-K.; Chang, Y.-T.; Korinek, M.; Chen, Y.-T.; Yang, Y.-T.; Leu, S.; Lin, I.-L.; Tang, C.-J.; Chiu, C.-C. The Regulations of Deubiquitinase USP15 and Its Pathophysiological Mechanisms in Diseases. Int. J. Mol. Sci. 2017, 18, 483.

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