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Mechanism of NF-κB action. The classic "canonical" NF-κB complex is a heterodimer of p50 and RelA, [1] as shown. NF-κB waits for activation in the cytosol, complexed with the inhibitory protein IκBα. Various extracellular signals can enter the cell via membrane receptors and activate the enzyme IκB kinase (IKK).
NF-κB has been detected in numerous cell types that express cytokines, chemokines, growth factors, cell adhesion molecules, and some acute phase proteins in health and in various disease states. NF-κB is activated by a wide variety of stimuli such as cytokines, oxidant-free radicals, inhaled particles, ultraviolet irradiation, and bacterial ...
NF-κB is a transcription factor that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NF-κB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions; over 200 ...
In resting cells, RelB is sequestered by the NF-κB precursor protein p100 in the cytoplasm. A select set of TNF-R superfamily members, including lymphotoxin β-receptor (LTβR), BAFF-R, CD40 and RANK, activate the non-canonical NF-κB pathway. In this pathway, NIK stimulates the processing of p100 into p52, which in association with RelB ...
LUBAC modulates signaling complexes activating the canonical NF-kB pathway in response to various stimuli (e.g., TNF, IL-1, CD40L) by adding M1-linked polyubiquitin chains to signaling proteins [2],. [12] Additionally, LUBAC has been shown to interact with PKC and NLRP3/ASC inflammasome [13],. [14]
TNFR2 can also activate the canonical NF-κB pathway, though this is less common than non-canonical NF-κB activation. The details of TNFR2's activation of the canonical NF-κB pathway are unknown. Presumably, TAK1 and IKK are recruited by the TRAF2 / TRAF1/3 / cIAP1/2 signalling complex, which in turn activates the canonical NF-κB pathway. [26]
Genetic ablation of the paracaspase gene in mice and biochemical studies have shown that paracaspase is a crucial protein for T and B lymphocytes activation. It has an important role in the activation of the transcription factor NF-κB, in the production of interleukin-2 (IL-2) and in T and B lymphocytes proliferation [8] [9] Two alternatively spliced transcript variants encoding different ...
Baeuerle deciphered the canonical pathway by which transcription factor NF-kappaB is activated and first described inhibitory subunit I-kappaB and the p65/RelA subunit. [2] [15] Baeuerle is said to be one of the inventors of the controversial NF-kappaB.