Ubiquitin-mediated activation of TAK1 and IKK

A. Adhikari, M. Xu, Z. J. Chen

Research output: Contribution to journalArticle

274 Citations (Scopus)

Abstract

Transforming growth factor β activated kinase-1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, has emerged as a key regulator of signal transduction cascades leading to the activation of the transcription factors nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). Stimulation of cells with cytokines and microbial pathogens results in the activation of TAK1, which subsequently activates the I-kappa B kinase complex (IKK) and mitogen-activated protein (MAP) kinases, culminating in the activation of NF-κB and AP-1, respectively. Recent studies have shown that polyubiquitination of signalling proteins through lysine (Lys)-63-linked polyubiquitin chains plays an important role in the activation of TAK1 and IKK. Unlike Lys-48-linked polyubiquitination, which normally targets proteins for degradation by the proteasome, Lys-63-linked polyubiquitin chains act as scaffolds to assemble protein kinase complexes and mediate their activation through proteasome-independent mechanisms. The concept of ubiquitin-mediated activation of protein kinases is supported by the discoveries of ubiquitination and deubiquitination enzymes as well as ubiquitin-binding proteins that function upstream of TAK1 and IKK. Recent biochemical and genetic studies provide further insights into the mechanism and function of ubiquitin signalling and these advances will be the focus of this review.

Original languageEnglish (US)
Pages (from-to)3214-3226
Number of pages13
JournalOncogene
Volume26
Issue number22
DOIs
StatePublished - May 14 2007

Fingerprint

Ubiquitin
Polyubiquitin
Lysine
NF-kappa B
Transcription Factor AP-1
Proteasome Endopeptidase Complex
Protein Kinases
I-kappa B Kinase
MAP Kinase Kinase Kinases
Ubiquitination
Transforming Growth Factors
Mitogen-Activated Protein Kinases
Proteolysis
Molecular Biology
Signal Transduction
Carrier Proteins
Transcription Factors
Phosphotransferases
Cytokines
Enzymes

Keywords

  • IKK
  • Kinase
  • NF-kappa B
  • TAK1
  • Ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Ubiquitin-mediated activation of TAK1 and IKK. / Adhikari, A.; Xu, M.; Chen, Z. J.

In: Oncogene, Vol. 26, No. 22, 14.05.2007, p. 3214-3226.

Research output: Contribution to journalArticle

Adhikari, A. ; Xu, M. ; Chen, Z. J. / Ubiquitin-mediated activation of TAK1 and IKK. In: Oncogene. 2007 ; Vol. 26, No. 22. pp. 3214-3226.
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