Apr 13, 2013

Atypical IκB proteins - nuclear modulators of NF-κB signaling

Cell Communication and Signaling : CCS
Marc SchusterIngo Schmitz

Abstract

Nuclear factor κB (NF-κB) controls a multitude of physiological processes such as cell differentiation, cytokine expression, survival and proliferation. Since NF-κB governs embryogenesis, tissue homeostasis and the functions of innate and adaptive immune cells it represents one of the most important and versatile signaling networks known. Its activity is regulated via the inhibitors of NF-κB signaling, the IκB proteins. Classical IκBs, like the prototypical protein IκBα, sequester NF-κB transcription factors in the cytoplasm by masking of their nuclear localization signals (NLS). Thus, binding of NF-κB to the DNA is inhibited. The accessibility of the NLS is controlled via the degradation of IκBα. Phosphorylation of the conserved serine residues 32 and 36 leads to polyubiquitination and subsequent proteasomal degradation. This process marks the central event of canonical NF-κB activation. Once their NLS is accessible, NF-κB transcription factors translocate into the nucleus, bind to the DNA and regulate the transcription of their respective target genes. Several studies described a distinct group of atypical IκB proteins, referred to as the BCL-3 subfamily. Those atypical IκBs show entirely different sub-cellular localizations,...Continue Reading

  • References77
  • Citations24

References

Mentioned in this Paper

Polyubiquitination
T-Lymphocyte
Cataract, Nuclear Progressive
Receptors, Antigen
Interleukin-1
Transcription, Genetic
Protein Phosphorylation
Cell Nucleus
Embryonic Development
Cell Differentiation Process

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