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NF-κB
Owing to its amenability to experimentation and its importance in disease, NF-κB has, for the past 25 years, served as a model for inducible transcription factors. NF-κB plays its most important and evolutionarily conserved role in the immune system, and much of our understanding of NF-κB is derived from the quest to decipher and manipulate the immune response. However, besides its role in the immune system, NF-κB also acts broadly to influence gene expression events that impact cell survival, differentiation, and proliferation. As a result of such broad effects on physiology, the dysregulation of NF-κB can lead to severe consequences, including numerous diseases.
The NF-κB network consists of five family member protein monomers (p65/RelA, RelB, cRel, p50, and p52) that form homodimers or heterodimers that bind DNA differentially and are regulated by two pathways: the canonical, NF-κB essential modulator (NEMO)-dependent pathway and the noncanonical, NEMO-independent pathway.NF-κB likely plays the most prominent role in the development and function of the immune system and, not surprisingly, when dysregulated, contributes to the pathophysiology of inflammatory disease.Activation of the NF-κB pathway is involved in the pathogenesis of chronic inflammatory diseases, such as asthma, rheumatoid arthritis, and inflammatory bowel disease. In addition, altered NF-κB regulation may be involved in other diseases such as atherosclerosis and Alzheimer’s disease and a variety of human cancers.
The NF-κB network consists of five family member protein monomers (p65/RelA, RelB, cRel, p50, and p52) that form homodimers or heterodimers that bind DNA differentially and are regulated by two pathways: the canonical, NF-κB essential modulator (NEMO)-dependent pathway and the noncanonical, NEMO-independent pathway.NF-κB likely plays the most prominent role in the development and function of the immune system and, not surprisingly, when dysregulated, contributes to the pathophysiology of inflammatory disease.Activation of the NF-κB pathway is involved in the pathogenesis of chronic inflammatory diseases, such as asthma, rheumatoid arthritis, and inflammatory bowel disease. In addition, altered NF-κB regulation may be involved in other diseases such as atherosclerosis and Alzheimer’s disease and a variety of human cancers.
References
1.Oeckinghaus A,et al. Nat Immunol. 2011;12(8):695–708.
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