24.5: NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB exists in the inactive state in the cytoplasm of the resting cells. The inhibitory protein, IκB, masks the nuclear localization signals of the NF-κB. On induction of cells by external stimuli - such as pathogens or reactive oxygen species - the IκB is tagged and subsequently degraded in the proteasome. The free NF-κB can then act as a transcriptional activator for its target genes in the cell nucleus. The activation of these genes then allows the cell to mount an appropriate physiological response.
NF-κB Function and Associated Diseases
Besides acting as a central mediator of immune responses in animals, studies have revealed several other roles of NF-κB. These include the regulation of cell proliferation and apoptosis, tumor formation, and multiple and diverse functions in the nervous system - such as learning and memory.
Additionally, the NF-κB signaling pathway also acts as a target for some viral as well as bacterial pathogens. Pathogens like HIV, HPV, and Yersinia pestis have developed strategies to exploit or interfere with the NF-κB signaling pathway to evade host defense mechanisms. Because of its diverse roles in animals, the NF-κB signaling pathway is an excellent therapeutic target.
