Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Immunol Res. 2008;42(1-3):3-18. doi: 10.1007/s12026-008-8025-1.

The IkappaB kinase complex: master regulator of NF-kappaB signaling.

Author information

  • 1Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street (OVH 200E), Philadelphia, PA, 19104-6045, USA.

Abstract

The Nuclear Factor-kappa B (NF-kappaB) family of transcription factors regulates the expression of a wide range of genes critical for immune and inflammatory responses, cell survival, immune development, and cell proliferation. Dysregulated NF-kappaB activity occurs in a number of chronic inflammatory diseases and certain types of cancers making NF-kappaB signaling an attractive target for the development of anti-inflammatory and anti-cancer drugs. A pivotal regulator of all inducible NF-kappaB signaling pathways is the IkappaB kinase (IKK) complex that consists of two kinases (IKKalpha and IKKbeta) and a regulatory subunit named NF-kappaB essential modulator (NEMO). Genetic analysis of the IKK complex has identified two separate pathways named the classical and non-canonical mechanisms that are dependent on either NEMO and IKKbeta (classical) or IKKalpha alone (non-canonical). To better understand the mechanisms that regulate IKK complex activity and to address the differential functions of IKKalpha and IKKbeta we have molecularly dissected the IKKs. We describe here how these studies have identified a unique inhibitor of pro-inflammatory NF-kappaB signaling, an unforeseen role for IKKalpha in the classical NF-kappaB pathway, and a novel functional domain in IKKbeta that is not present in IKKalpha.

PMID:
18626576
[PubMed - indexed for MEDLINE]
PMCID:
PMC2965074
Free PMC Article

Images from this publication.See all images (3)Free text

Fig. 1
Fig. 2
Fig. 3
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Springer Icon for PubMed Central
    Loading ...
    Write to the Help Desk