文章基本信息

标题：Regulation of the Nuclear Factor (NF)-κB Pathway by ISGylation
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作者：Miki Minakawa ; Takayuki Sone ; Tomoharu Takeuchi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：12
页码：2223-2227
DOI：10.1248/bpb.31.2223
出版社：The Pharmaceutical Society of Japan
摘要：Post-translational modification with ISG15 (interferon-stimulated gene 15 kDa) (ISGylation) is mediated by a sequential reaction similar to ubiquitination, and various target proteins for ISGylation have been identified. We previously reported that ISGylation of the E2 ubiquitin-conjugating enzyme Ubc13 suppresses its E2 activity. Ubc13 forms a heterodimer with Uev1A, a ubiquitin-conjugating enzyme variant, and the Ubc13–Uev1A complex catalyzes the assembly of a Lys63-linked polyubiquitin chain, which plays a non-proteolytic role in the nuclear factor (NF)-κB pathway. In this study, we examined the effect of ISGylation on tumor necrosis factor receptor-associated factor (TRAF)-6/transforming growth factor β-activated kinase (TAK)-1-dependent NF-κB activation. We found that expression of the ISGylation system suppresses NF-κB activation via TRAF6 and TAK1 and that the level of polyubiquitinated TRAF6 is reduced by expression of the ISGylation system. Taken together, the results suggest that the NF-κB pathway is negatively regulated by ISGylation.
关键词：interferon-stimulated gene;post-translational modification;nuclear factor-κB;tumor necrosis factor receptor-associated factor 6;ubiquitin-conjugating enzyme