The NF-kappaB family of transcription factors and its regulation
- PMID: 20066092
- PMCID: PMC2773619
- DOI: 10.1101/cshperspect.a000034
The NF-kappaB family of transcription factors and its regulation
Abstract
Nuclear factor-kappaB (NF-kappaB) consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. Inducible NF-kappaB activation depends on phosphorylation-induced proteosomal degradation of the inhibitor of NF-kappaB proteins (IkappaBs), which retain inactive NF-kappaB dimers in the cytosol in unstimulated cells. The majority of the diverse signaling pathways that lead to NF-kappaB activation converge on the IkappaB kinase (IKK) complex, which is responsible for IkappaB phosphorylation and is essential for signal transduction to NF-kappaB. Additional regulation of NF-kappaB activity is achieved through various post-translational modifications of the core components of the NF-kappaB signaling pathways. In addition to cytosolic modifications of IKK and IkappaB proteins, as well as other pathway-specific mediators, the transcription factors are themselves extensively modified. Tremendous progress has been made over the last two decades in unraveling the elaborate regulatory networks that control the NF-kappaB response. This has made the NF-kappaB pathway a paradigm for understanding general principles of signal transduction and gene regulation.
Figures
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References
-
- Amir RE, Haecker H, Karin M, Ciechanover A 2004. Mechanism of processing of the NF-κ B2 p100 precursor: Identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of NEDD8-modification on the SCF(β-TrCP) ubiquitin ligase. Oncogene 23:2540–2547 - PubMed
-
- Anest V, Hanson JL, Cogswell PC, Steinbrecher KA, Strahl BD, Baldwin AS 2003. A nucleosomal function for IκB kinase-α in NF-κB-dependent gene expression. Nature 423:659–663 - PubMed
-
- Baeuerle PA, Henkel T 1994. Function and activation of NF-κ B in the immune system. Annu Rev Immunol 12:141–179 - PubMed
-
- Baldwin AS Jr 1996. The NF-κ B and I κ B proteins: New discoveries and insights. Annu Rev Immunol 14:649–683 - PubMed
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