NFKB Signaling Pathway

Preferred Label : NFKB Signaling Pathway;

NCIt related terms : NF-kB Signaling Pathway;

Alternative definition : BIOCARTA: Nuclear factor kB (NF-kB) is a nuclear transcription factor that regulates expression of a large number of genes that are critical for the regulation of apoptosis, viral replication, tumorigenesis, inflammation, and various autoimmune diseases. The activation of NF-kB is thought to be part of a stress response as it is activated by a variety of stimuli that include growth factors, cytokines, lymphokines, UV, pharmacological agents, and stress. In its inactive form, NF-kB is sequestered in the cytoplasm, bound by members of the IkB family of inhibitor proteins, which include IkBa, IkBb, IkBg, and IkBe. The various stimuli that activate NF-kB cause phosphorylation of IkB, which is followed by its ubiquitination and subsequent degradation. This results in the exposure of the nuclear localization signals (NLS) on NF-kB subunits and the subsequent translocation of the molecule to the nucleus. In the nucleus, NF-kB binds with a consensus sequence (5'GGGACTTTCC-3') of various genes and thus activates their transcription. IkB proteins are phosphorylated by IkB kinase complex consisting of at least three proteins; IKK1/IKKa, IKK2/IKKb, and IKK3/IKKg. These enzymes phosphorylate IkB leading to its ubiquitination and degradation. Tumor necrosis factor (TNF) which is the best-studied activator binds to its receptor and recruits a protein called TNF receptor death domain (TRADD). TRADD binds to the TNF receptor-associated factor 2 (TRAF-2) that recruits NF-kB-inducible kinase (NIK). Both IKK1 and IKK2 have canonical sequences that can be phosphorylated by the MAP kinase NIK/MEKK1 and both kinases can independently phosphorylate IkBa or IkBb. TRAF-2 also interacts with A20, a zinc finger protein whose expression is induced by agents that activate NF-kB. A20 functions to block TRAF2-mediated NF-kB activation. A20 also inhibits TNF and IL-1 induced activation of NF-kB suggesting that it may act as a general inhibitor of NF-kB activation. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_nfkbPathway;

Details

Origin ID

C39163;

UMLS CUI

C1513838;

Semantic type(s)
- Genetic Function [UMLS semantic type]
has_gene_product_element
- FAS-Associated Death Domain Protein [NCIt concept]
- Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Alpha [NCIt concept]
- Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Beta [NCIt concept]
- Interleukin-1 Alpha [NCIt concept]
- Interleukin-1 Receptor Type 1 [NCIt concept]
- Interleukin-1 Receptor-Associated Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase 14 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase 7 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 [NCIt concept]
- NF-Kappa-B Inhibitor Alpha [NCIt concept]
- Nuclear Factor NF-kappa-B p105 Subunit [NCIt concept]
- Receptor-Interacting Serine/Threonine-Protein Kinase 1 [NCIt concept]
- TGF-Beta-Activated Kinase 1 and MAP3K7-Binding Protein 1 [NCIt concept]
- TNF Receptor-Associated Factor 6 [NCIt concept]
- Toll-Like Receptor 4 [NCIt concept]
- Transcription Factor p65 [NCIt concept]
- Tumor Necrosis Factor [NCIt concept]
- Tumor Necrosis Factor Receptor 1-Associated DEATH Domain Protein [NCIt concept]
- Tumor Necrosis Factor Receptor Superfamily Member 1A [NCIt concept]
pathway_has_gene_element
- CHUK wt Allele [NCIt concept]
- FADD wt Allele [NCIt concept]
- IKBKB wt Allele [NCIt concept]
- IL1A wt Allele [NCIt concept]
- IL1R1 wt Allele [NCIt concept]
- IRAK1 wt Allele [NCIt concept]
- MAP3K1 wt Allele [NCIt concept]
- MAP3K14 wt Allele [NCIt concept]
- MAP3K7 wt Allele [NCIt concept]
- MAP4K4 wt Allele [NCIt concept]
- NFKB1 wt Allele [NCIt concept]
- NFKBIA wt Allele [NCIt concept]
- RELA wt Allele [NCIt concept]
- RIPK1 wt Allele [NCIt concept]
- TAB1 wt Allele [NCIt concept]
- TLR4 wt Allele [NCIt concept]
- TNF wt Allele [NCIt concept]
- TNFRSF1A wt Allele [NCIt concept]
- TRADD wt Allele [NCIt concept]
- TRAF6 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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