IκB kinase ε (IKKε): a therapeutic target in inflammation and cancer

Biochem Pharmacol. 2013 Apr 1;85(7):873-80. doi: 10.1016/j.bcp.2013.01.007. Epub 2013 Jan 17.

Abstract

The innate immune system forms our first line of defense against invading pathogens and relies for a major part on the activation of two transcription factors, NF-κB and IRF3. Signaling pathways that activate these transcription factors are intertwined at the level of the canonical IκB kinases (IKKα, IKKβ) and non-canonical IKK-related kinases (IKKε, TBK1). Recently, significant progress has been made in understanding the function and mechanism of action of IKKε in immune signaling. In addition, IKKε impacts on cell proliferation and transformation, and is thereby also classified as an oncogene. Studies with IKKε knockout mice have illustrated a key role for IKKε in inflammatory and metabolic diseases. In this review we will highlight the mechanisms by which IKKε impacts on signaling pathways involved in disease development and discuss its potential as a novel therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Enzyme Activation
  • Humans
  • I-kappa B Kinase / antagonists & inhibitors
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • Inflammation / drug therapy
  • Inflammation / enzymology*
  • Interferon Regulatory Factors / metabolism
  • Metabolic Diseases / drug therapy
  • Metabolic Diseases / enzymology
  • Mice
  • Mice, Knockout
  • Molecular Targeted Therapy
  • NF-kappa B / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction

Substances

  • Interferon Regulatory Factors
  • NF-kappa B
  • Protein Serine-Threonine Kinases
  • TBK1 protein, human
  • I-kappa B Kinase