Regulation of the Nuclear Factor (NF)-κB Pathway by ISGylation(Molecular and Cell Biology)

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概要

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• Post-translational modification with ISG15 (interferon-stimulated gene 15kDa) (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.

• 公益社団法人日本薬学会の論文
• 2008-12-01

著者

• YOKOSAWA Hideyoshi

  Department of Biochemistry, Faculty of Pharmacological Science, Hokkaido University

• Minakawa Miki

  Department Of Biochemistry Graduate School Of Pharmaceutical Sciences Hokkaido University

• Yokosawa Hideyoshi

  Department Of Biochemistry Graduate School Of Pharmaceutical Sciences Hokkaido University:riken Brai

• SONE Takayuki

  Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University

• TAKEUCHI Tomoharu

  Department of Biological Chemistry, Teikyo University School of Pharmaceutical Sciences

• Sone Takayuki

  Department Of Biochemistry Graduate School Of Pharmaceutical Sciences Hokkaido University

• Takeuchi Tomoharu

  Department Of Biological Chemistry Teikyo University School Of Pharmaceutical Sciences

• Takeuchi Tomoharu

  Department Of Biochemistry Graduate School Of Pharmaceutical Sciences Hokkaido University

• Yokosawa Hideyoshi

  Department Of Biochemistry Faculty Of Pharmaceutical Sciences Hokkaido University

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