IKBKB
Protein IKBKB PDB 3BRT.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesIKBKB, IKK-beta, IKK2, IKKB, IMD15, NFKBIKB, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta, inhibitor of nuclear factor kappa B kinase subunit beta, IMD15A, IMD15B
External IDsOMIM: 603258 MGI: 1338071 HomoloGene: 7782 GeneCards: IKBKB
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001190720
NM_001190721
NM_001190722
NM_001242778
NM_001556

NM_001159774
NM_010546

RefSeq (protein)

NP_001177649
NP_001229707
NP_001547

NP_001153246
NP_034676

Location (UCSC)Chr 8: 42.27 – 42.33 MbChr 8: 23.15 – 23.2 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

Function

Main article: IκB kinase

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

Clinical significance

IKK-β plays a significant role in brain cells following a stroke.[5] If NF-κB activation by IKK-β is blocked, damaged cells within the brain stay alive, and according to a study performed by the University of Heidelberg and the University of Ulm, the cells even appear to make some recovery.[6]

Inhibition of IKK and IKK-related kinases has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer.[7] The small-molecule inhibitor of IKK2 SAR113945, developed by Sanofi-Aventis, was evaluated in patients with knee osteoarthritis.[8]

Model organisms

Model organisms have been used in the study of IKK-β function. The size of an infarct, or tissue killed or damaged by ischemia, is reduced in mice in which IKK-β has been blocked.[9] Additionally, experimental mice with an overactive form of IKK-β experience loss of many more neurons than normal mice after a stroke-simulating event.[6] Researchers found a molecule that could block the signaling of IKK-β for up to four and a half hours.[10] In another study, researchers found that inhibiting IKK-β prevented kidney and wasting diseases in an animal model used to study wasting diseases of human AIDS sufferers.[11]

A conditional knockout mouse line, called Ikbkbtm1a(EUCOMM)Wtsi[16][17] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[18][19][20]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[14][21] Twenty six tests were carried out and two phenotypes were reported. A reduced number of homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice, and no significant abnormalities were observed in these animals.[14]

Interactions

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

References

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See also