Ubiquitin-mediated regulation of protein kinases in nfκb signaling

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Phosphorylation regulates protein ubiquitination and subsequent degradation by the proteasome. Ubiquitination can also regulate protein phosphorylation through both proteasome-dependent and independent mechanisms. This chapter discusses the current understanding of ubiquitin-mediated regulation of protein kinases in different pathways leading to NF?B activation, focusing on those emanating from tumor necrosis factor receptors (TNFRs), interleukin-1 receptors (IL-1Rs), and Toll-like receptors (TLRs). Mounting evidence supports a key role of polyubiquitination in the activation of TAK1, IKK, and MAP kinases in immune and inflammatory pathways. The regulatory role of ubiquitin is not limited to protein kinase activation. It is now clear that monoubiquitination and polyubiquitination regulate many cellular processes, including membrane trafficking, DNA repair, and gene transcription through mechanisms independent of protein degradation. In almost all cases, ubiquitin signaling is mediated by a network of interactions between ubiquitinated proteins and ubiquitin-binding proteins. As evidenced by the success of proteasome inhibitors in the treatment of multiple myeloma, increased understanding of both proteolytic and non-proteolytic functions of ubiquitin is likely to facilitate the development of potent and specific therapeutics for the treatment of various human diseases.

Original languageEnglish (US)
Title of host publicationHandbook of Cell Signaling, 2/e
PublisherElsevier Inc.
Pages633-644
Number of pages12
Volume2
ISBN (Print)9780123741455
DOIs
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Xu, M., & Chen, Z. J. (2010). Ubiquitin-mediated regulation of protein kinases in nfκb signaling. In Handbook of Cell Signaling, 2/e (Vol. 2, pp. 633-644). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-374145-5.00083-8