AI Article Synopsis
- Post-translational modification known as ISGylation (involving ISG15) is similar to ubiquitination and can modify various proteins.
- ISGylation of the enzyme Ubc13 decreases its activity, affecting its ability to form a complex with Uev1A that is crucial for NF-kappaB signaling.
- The study shows that ISGylation inhibits NF-kappaB activation by reducing polyubiquitinated TRAF6 levels, indicating it has a negative regulatory role in this pathway.
Article Abstract
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)-kappaB pathway. In this study, we examined the effect of ISGylation on tumor necrosis factor receptor-associated factor (TRAF)-6/transforming growth factor beta-activated kinase (TAK)-1-dependent NF-kappaB activation. We found that expression of the ISGylation system suppresses NF-kappaB 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-kappaB pathway is negatively regulated by ISGylation.
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| http://dx.doi.org/10.1248/bpb.31.2223 | DOI Listing |
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