Phosphorylation of NF-kappaB and IkappaB Proteins: Implications in Cancer and Inflammation

Trends Biochem Sci. 2005 Jan;30(1):43-52. doi: 10.1016/j.tibs.2004.11.009.

Abstract

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis. Activation of NF-kappaB mainly occurs via IkappaB kinase (IKK)-mediated phosphorylation of inhibitory molecules, including IkappaBalpha. Optimal induction of NF-kappaB target genes also requires phosphorylation of NF-kappaB proteins, such as p65, within their transactivation domain by a variety of kinases in response to distinct stimuli. Whether, and how, phosphorylation modulates the function of other NF-kappaB and IkappaB proteins, such as B-cell lymphoma 3, remains unclear. The identification and characterization of all the kinases known to phosphorylate NF-kappaB and IkappaB proteins are described here. Because deregulation of NF-kappaB and IkappaB phosphorylations is a hallmark of chronic inflammatory diseases and cancer, newly designed drugs targeting these constitutively activated signalling pathways represent promising therapeutic tools.

Publication types

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

MeSH terms

  • Animals
  • Drug Design
  • Gene Expression Regulation, Leukemic*
  • Humans
  • I-kappa B Proteins / metabolism*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism*
  • Lymphoma, B-Cell / pathology
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Signal Transduction* / physiology
  • Transcription Factor RelA

Substances

  • I-kappa B Proteins
  • NF-kappa B
  • Transcription Factor RelA