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NF-kB Pathway Image

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NF-kB Pathway

Overview of NF-kB Pathway

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a heterodimer composed of homo- and heterodimers of five members of the Rel family including NFKB1 (p50), NFkB2 (p52), RelA (p65), RelB, and c-Rel (Rel). NF-κB can be found in almost all animal cell types and functions in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. There are a variety of inducers which can activate NF-κB, including LPS (Lipopolysaccharides) or inflammatory cytokines such as TNF (Tumour Necrosis Factor) or IL-1 (Interleukin-1), growth factors, lymphokines, oxidant-free radicals, inhaled particles, viral infection or expression of certain viral or bacterial gene products, UV irradiation, B or T-Cell activation, and by other physiological and non physiological stimuli.

When inactivated, NF-κB is located in the cytosol complexed with the inhibitory protein IκBα. After the enzyme IκB kinase (IKK) is activated, IKK phosphorylates the IκBα protein, which results in ubiquitination, dissociation of IκBα from NF-κB, and eventual degradation of IκBα by the proteosome. The activated NF-κB is then translocated into the nucleus where it binds to specific sequences of DNA called response elements (RE). The DNA/NF-κB complex then recruits other proteins such as coactivators and RNA polymerase, which transcribe downstream DNA into mRNA, which, in turn, is translated into protein, which results in a change of cell function.

In the non-canonical pathway, a subset of receptors belonging to the TNFR superfamily activate the kinase NIK through an unknown mechanism. NIK then phosphorylates IKKα, which in turn phosphorylates the NF-κB precursor p100. P100 is subsequently polyubiquitinated and then processed to the mature subunit p52 by the proteasome. P52 and its binding partner Rel-B translocate to the nucleus to turn on genes that are important for the maturation of B cells.

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