Transcriptional regulation via the NF-κB signaling module

A. Hoffmann, G. Natoli, G. Ghosh

Research output: Contribution to journalArticle

Abstract

Stimulus-induced nuclear factor-κB (NF-κB) activity, the central mediator of inflammatory responses and immune function, comprises a family of dimeric transcription factors that regulate diverse gene expression programs consisting of hundreds of genes. A family of inhibitor of κB (IκB) proteins controls NF-κB DNA-binding activity and nuclear localization. IκB protein metabolism is intricately regulated through stimulus-induced degradation and feedback re-synthesis, which allows for dynamic control of NF-κB activity. This network of interactions has been termed the NF-κB signaling module. Here, we summarize the current understanding of the molecular structures and biochemical mechanisms that determine NF-κB dimer formation and the signal-processing characteristics of the signaling module. We identify NF-κB-κB site interaction specificities and dynamic control of NF-κB activity as mechanisms that generate specificity in transcriptional regulation. We discuss examples of gene regulation that illustrate how these mechanisms may interface with other transcription regulators and promoter-associated events, and how these mechanisms suggest regulatory principles for NF-κB-mediated gene activation.

Original languageEnglish
Pages (from-to)6706-6716
Number of pages11
JournalOncogene
Volume25
Issue number51
DOIs
Publication statusPublished - Oct 30 2006

Keywords

  • Combinatorial control
  • Dynamic control
  • IkappaB
  • NF-kappaB
  • Signal transduction
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'Transcriptional regulation via the NF-κB signaling module'. Together they form a unique fingerprint.

  • Cite this