|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
The IκB kinase enzyme complex is part of the upstream NF-κB signal transduction cascade. The IκBα (inhibitor of kappa B) protein inactivates the NF-κB transcription factor by masking the nuclear localization signals (NLS) of NF-κB proteins and keeping them sequestered in an inactive state in the cytoplasm. IKK specifically, phosphorylates the inhibitory IκBα protein. This phosphorylation results in the dissociation of IκBα from NF-κB. NF-κB, which is now free migrates into the nucleus and activates the expression of at least 150 genes; some of which are anti-apoptotic.
- ATP + IκB protein <math>\rightleftharpoons</math> ADP + IκB phosphoprotein
This enzyme belongs to the family of transferases, specifically those transferring a phosphate group to the sidechain oxygen atom of serine or threonine residues in proteins (protein-serine/threonine kinases). The systematic name of this enzyme class is ATP:[IκB protein] phosphotransferase.
The IκB kinase complex is composed of three subunits each encoded by a separate gene:
- IKK-α (also known as IKK1) (CHUK)
- IKK-β (also known as IKK2) (IKBKB)
- IKK-γ (also known as NEMO) (IKBKG)
The α- and β-subunits together are catalytically active whereas the γ-subunit serves a regulatory function.
This enzyme participates in 15 pathways related to metabolism: MapK signaling, apoptosis, Toll-like receptor signaling, T-cell receptor signaling, B-cell receptor signaling, insulin signaling, adipokine signaling, Type 2 diabetes mellitus, epithelial cell signaling in helicobacter pylori, pancreatic cancer, prostate cancer, chronic myeloid leukemia, acute myeloid leukemia, and small cell lung cancer.
Inhibition of IκB kinase (IKK) and IKK-related kinases, IKBKE (IKKε) and TANK-binding kinase 1 (TBK1), has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer. The small-molecule inhibitor of IKK-β SAR113945, developed by Sanofi-Aventis, was evaluated in patients with knee osteoarthritis.
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