IKK2

IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a is_associated_with::protein that in humans is encoded by the IKBKB (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta) is_associated_with::gene.

Function
IKK-β is an is_associated_with::enzyme that serves as a is_associated_with::protein subunit of is_associated_with::IκB kinase, which is a component of the is_associated_with::cytokine-activated is_associated_with::intracellular signaling pathway involved in triggering immune responses. IKK's activity causes activation of a is_associated_with::transcription factor known as Nuclear Transcription factor kappa-B or is_associated_with::NF-κB. Activated IKK-β phosphorylates a protein called the inhibitor of NF-κB, IκB (is_associated_with::IκBα), which binds NF-κB to inhibit its function. Phosphorylated IκB is degraded via the is_associated_with::ubiquitination pathway, freeing NF-κB, and allowing its entry into the nucleus of the cell where it activates various genes involved in is_associated_with::inflammation and other immune responses.

Clinical significance
IKK-β plays a significant role in is_associated_with::brain cells following a is_associated_with::stroke. If is_associated_with::NF-κB activation by IKK-β is blocked, damaged cells within the brain stay alive, and according to a study performed by the is_associated_with::University of Heidelberg and the University of Ulm, the cells even appear to make some recovery.

Inhibition of IKK and IKK-related kinases has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer. The small-molecule inhibitor of IKK2 SAR113945, developed by Sanofi-Aventis, was evaluated in patients with knee osteoarthritis.

Model organism s
is_associated_with::Model organisms have been used in the study of IKK-β function. The size of an is_associated_with::infarct, or tissue killed or damaged by is_associated_with::ischemia, is reduced in mice in which IKK-β has been blocked. Additionally, experimental mice with an overactive form of IKK-β experience loss of many more neurons than normal mice after a stroke-simulating event. Researchers found a molecule that could block the signaling of IKK-β for up to four and a half hours. In another study, researchers found that inhibiting IKK-β prevented kidney and is_associated_with::wasting diseases in an is_associated_with::animal model used to study wasting diseases of human is_associated_with::AIDS sufferers.

A conditional is_associated_with::knockout mouse line, called Ikbkbtm1a(EUCOMM)Wtsi was generated as part of the is_associated_with::International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the is_associated_with::Wellcome Trust Sanger Institute.

Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Twenty six tests were carried out and two is_associated_with::phenotypes were reported. A reduced number of is_associated_with::homozygous is_associated_with::mutant embryos were identified during gestation, and none survived until is_associated_with::weaning. The remaining tests were carried out on is_associated_with::heterozygous mutant adult mice, and no significant abnormalities were observed in these animals.

Interactions
IKK-β (IKBKB) has been shown to interact with


 * is_associated_with::CDC37,
 * is_associated_with::CHUK
 * CTNNB1,
 * is_associated_with::FANCA,
 * is_associated_with::IKBKG
 * is_associated_with::IRAK1,
 * NFKBIA,
 * is_associated_with::MAP3K14,
 * is_associated_with::NFKB1,
 * is_associated_with::NFKBIB,
 * NCOA3,
 * is_associated_with::PPM1B,
 * is_associated_with::TNFRSF1A, and
 * is_associated_with::TRAF2.