Open Access

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

  • Authors:
    • Naoko Yagishita
    • Satoko Aratani
    • Craig Leach
    • Tetsuya Amano
    • Yoshihisa Yamano
    • Ko Nakatani
    • Kusuki Nishioka
    • Toshihiro Nakajima
  • View Affiliations

  • Published online on: September 18, 2012     https://doi.org/10.3892/ijmm.2012.1129
  • Pages: 1281-1286
  • Copyright: © Yagishita et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Rheumatoid arthritis (RA) significantly affects quality of life. We recently cloned synoviolin, a RING-type E3 ubiquitin ligase implicated in the endoplasmic reticulum-associated degradation (ERAD) pathway. Synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of RA. Inhibition of synoviolin 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 synoviolin autoubiquitination activity. We identified two classes of small molecules, named LS-101 and LS-102, which inhibited synoviolin activity. LS-102 selectively inhibited synoviolin enzymatic activity, while LS-101 inhibited a broad array of RING-type E3 ligases. Moreover, these inhibitors suppressed the proliferation of rheumatoid synovial cells, and significantly reduced the severity of disease in a mouse model of RA. Our results suggest that inhibition of synoviolin is a potentially useful approach in the treatment of RA.
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December 2012
Volume 30 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yagishita N, Aratani S, Leach C, Amano T, Yamano Y, Nakatani K, Nishioka K and Nakajima T: RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis. Int J Mol Med 30: 1281-1286, 2012
APA
Yagishita, N., Aratani, S., Leach, C., Amano, T., Yamano, Y., Nakatani, K. ... Nakajima, T. (2012). RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis. International Journal of Molecular Medicine, 30, 1281-1286. https://doi.org/10.3892/ijmm.2012.1129
MLA
Yagishita, N., Aratani, S., Leach, C., Amano, T., Yamano, Y., Nakatani, K., Nishioka, K., Nakajima, T."RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis". International Journal of Molecular Medicine 30.6 (2012): 1281-1286.
Chicago
Yagishita, N., Aratani, S., Leach, C., Amano, T., Yamano, Y., Nakatani, K., Nishioka, K., Nakajima, T."RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis". International Journal of Molecular Medicine 30, no. 6 (2012): 1281-1286. https://doi.org/10.3892/ijmm.2012.1129