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Updated: Jun 18, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
Delineating role of ubiquitination on nuclear factor-kappa B pathway by a computational modeling approach
Jungsul Lee1, Kyungsun Choi, Chulhee Choi
1Cell Signaling and BioImaging Laboratory, Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Republic of Korea.
Abstract:
Mutant ubiquitin found in neurodegenerative diseases has been thought to hamper activation of transcription factor nuclear factor-kappa B (NF-kappaB) by inhibiting ubiquitin-proteasome system (UPS). It has been reported that ubiquitin also is involved in signal transduction in an UPS-independent manner. We used a modeling and simulation approach to delineate the roles of ubiquitin on NF-kappaB activation. Inhibition of proteasome complex increased maximal activation of IKK mainly by decreasing the UPS efficiency. On the contrary, mutant ubiquitin decreased maximal activity of IKK. Computational modeling showed that the inhibition effect of mutant ubiquitin is mainly attributed to decreased activity of UPS-independent function of ubiquitin. Collectively, our results suggest that mutant ubiquitin affects NF-kappaB activation in an UPS-independent manner.
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