NDLI: RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis.

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RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis.

Content Provider	Europe PMC
Author	YAGISHITA, NAOKO ARATANI, SATOKO LEACH, CRAIG AMANO, TETSUYA YAMANO, YOSHIHISA NAKATANI, KO NISHIOKA, KUSUKI NAKAJIMA, TOSHIHIRO
Copyright Year	2012
Abstract	Rheumatoid arthritis (RA) significantly affects quality of life. We recently clonedsynoviolin, a RING-type E3 ubiquitin ligase implicated in the endoplasmicreticulum-associated degradation (ERAD) pathway. Synoviolin is highly expressed inrheumatoid synovial cells and may be involved in the pathogenesis of RA. Inhibition ofsynoviolin activity is a potentially useful therapeutic approach for the treatment of RA.We conducted a high-throughput screen of small molecules to find inhibitors of synoviolinautoubiquitination activity. We identified two classes of small molecules, named LS-101and LS-102, which inhibited synoviolin activity. LS-102 selectively inhibited synoviolinenzymatic activity, while LS-101 inhibited a broad array of RING-type E3 ligases.Moreover, these inhibitors suppressed the proliferation of rheumatoid synovial cells, andsignificantly reduced the severity of disease in a mouse model of RA. Our results suggestthat inhibition of synoviolin is a potentially useful approach in the treatment of RA.
ISSN	11073756
Journal	International Journal of Molecular Medicine
Volume Number	30
PubMed Central reference number	PMC4042867
Issue Number	6
PubMed reference number	22992760
e-ISSN	1791244X
DOI	10.3892/ijmm.2012.1129
Language	English
Publisher	D.A. Spandidos
Publisher Date	2012-09-18
Access Restriction	Open
Rights License	This is an open-access article licensed under a Creative CommonsAttribution-NonCommercial 3.0 Unported License. The article may be redistributed,reproduced, and reused for non-commercial purposes, provided the original source isproperly cited. Copyright © 2012, Spandidos Publications
Subject Keyword	rheumatoid arthritis synoviolin E3 ubiquitin ligase endoplasmic reticulum associated degradation inhibitor
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine

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