The role of ubiquitin in NF-κB regulatory pathways

Brian Skaug, Xiaomo Jiang, Zhijian J. Chen

Research output: Contribution to journalReview article

360 Scopus citations

Abstract

Nuclear factor kappa enhancer binding protein (NF-κB) regulates diverse biological processes including immunity, inflammation, and apoptosis. A vast array of cellular stimuli converges on NF-κB, and ubiquitination plays an essential role in the coordination of these signals to regulate NF-κB activity. At least three steps in NF-κB activation directly involve ubiquitination: proteasomal degradation of inhibitor of NF-κB (IκB), processing of NF-κB precursors, and activation of the transforming growth factor (TGF)-β-activated kinase (TAK1) and IκB kinase (IKK) complexes. In this review, we discuss recent advances in the identification and characterization of ubiquitination and deubiquitination machinery that regulate NF-κB. Particular emphasis is given to proteasome-independent functions of ubiquitin, specifically its role in the activation of protein kinase complexes and in coordination of cell survival and apoptosis signals downstream of tumor necrosis factor α (TNFα).

Original languageEnglish (US)
Pages (from-to)769-796
Number of pages28
JournalAnnual review of biochemistry
Volume78
DOIs
StatePublished - Jul 24 2009

Keywords

  • Apoptosis
  • Deubiquitination
  • IKK
  • TAK1

ASJC Scopus subject areas

  • Biochemistry

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