|MoBio||Regulation of NF-kB||Chapter 4|
Nuclear factor-κB (NF-κB) is a ubiquitous transcription factor that controls the expression of genes involved in immune responses, apoptosis, and cell cycle. Incorrect regulation of NF-κB may cause inflammatory and autoimmune diseases, viral infection and cancer. Five mammalian NF-κB family members have been identified:
They all share a highly conserved Rel homology domain, responsible for their dimerization and binding to DNA and IκB (inhibitor of NF-κB). The transcription factor NF-κB works only when two members form a dimer. The most abundant activated form consists of a p50 or p52 subunit and a p65 subunit.
NF-κB can be activated by a variety of stimuli, including cytokines (such as TNF-α and IL-1), T and B cell mitogens, viral proteins, and stress inducers (such as reactive oxygen species or UV radiation). In the cytoplasm, NF-κB is inhibited by IκB. Upstream activating signal (e.g., binding of TNF-α to its receptor) may cause phosphorylation of IκB by IKK (IκB kinase). This triggers the degradation of IκB through the ubiquitin system, where the target molecule is masked by a chain of ubiquitins for degradation by the 26S protesome. The free NF-κB can then translocate to the nucleus and activate transcription.
Figure 4-H-4. Activation of NF-κB.