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Biochem Biophys Res Commun. 2010 Jan 1;391(1):33-7. doi: 10.1016/j.bbrc.2009.10.155. Epub 2009 Nov 4.

Delineating role of ubiquitination on nuclear factor-kappa B pathway by a computational modeling approach.

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  • 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.

Copyright 2009 Elsevier Inc. All rights reserved.

PMID:
19895789
[PubMed - indexed for MEDLINE]
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