Nuclear ubiquitin ligases, NF-κB degradation, and the control of inflammation

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Abstract

Transcriptional control of the vast majority of genes involved in the inflammatory response requires the nuclear factor κB (NF-κB) family of transcription factors. Stimulation and termination of NF-κB activity are subject to stringent spatiotemporal control. According to the classical model of NF-κB regulation, both activation and termination mechanisms are centered on inhibitor of NF-κB (IκB) proteins. Whereas activation of NF-κB requires degradation of the I?Bs, the main mechanism respon- sible for termination of NF-κB activity is the resynthesis of a specific IκB, IκBα, which sequesters NF-κB dimers in the nucleus and translocates them to the cyto- plasm in an inactive form. Studies now show that an additional mechanism that is required to prevent the uncontrolled activity of NF-κB proteins is their nuclear degradation. At least two E3 ubiquitin ligases, one of which seems to be essential for control of nuclear NF-κB p65 (also known as RelA) in myeloid cells, have been identified. Moreover, additional evidence indicates that individual NF-κB dimers with particular activating or repressive properties may be differentially controlled by nuclear degradation, thus paving the way for the exploitation of NF-κB degradation pathways for therapeutic purposes.

Original languageEnglish
Article number11pe1
JournalScience Signaling
Volume1
Issue number1
DOIs
Publication statusPublished - Jan 8 2008

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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