IKK2

IKBKB
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases IKBKB, IKK-beta, IKK2, IKKB, IMD15, NFKBIKB, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta
External IDs OMIM: 603258 MGI: 1338071 HomoloGene: 7782 GeneCards: IKBKB
Targeted by Drug
bms-345541 free base[1]
RNA expression pattern




More reference expression data
Orthologs
Species Human Mouse
Entrez

3551

16150

Ensembl

ENSG00000104365

ENSMUSG00000031537

UniProt

O14920

O88351

RefSeq (mRNA)

NM_001190720
NM_001190721
NM_001190722
NM_001242778
NM_001556

NM_001159774
NM_010546

RefSeq (protein)

NP_001177649.1
NP_001229707.1
NP_001547.1

NP_034676.1

Location (UCSC) Chr 8: 42.27 – 42.33 Mb Chr 8: 22.66 – 22.71 Mb
PubMed search [2] [3]
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. 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.[4]

Inhibition of IKK and IKK-related kinases has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer.[5][5] The small-molecule inhibitor of IKK2 SAR113945, developed by Sanofi-Aventis, was evaluated in patients with knee osteoarthritis.[6]

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.[7] Additionally, experimental mice with an overactive form of IKK-β experience loss of many more neurons than normal mice after a stroke-simulating event.[4] Researchers found a molecule that could block the signaling of IKK-β for up to four and a half hours.[8] 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.[9]

A conditional knockout mouse line, called Ikbkbtm1a(EUCOMM)Wtsi[14][15] 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.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] 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.[12]

Interactions

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

References

  1. "Drugs that physically interact with Inhibitor of nuclear factor kappa-B kinase subunit beta view/edit references on wikidata".
  2. "Human PubMed Reference:".
  3. "Mouse PubMed Reference:".
  4. 1 2 BBC News. 14 November 2005. Stroke 'cell-death trigger' found. Retrieved on June 28, 2007.
  5. 1 2 Llona-Minguez S, Baiget J, Mackay SP (2013). "Small-molecule inhibitors of IκB kinase (IKK) and IKK-related kinases". Pharm. Pat. Anal. 2 (4): 481–498. doi:10.4155/ppa.13.31. PMID 24237125.
  6. "SAR113945 published clinical trials".
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  25. 1 2 Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ (October 2000). "Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain". Cell. 103 (2): 351–61. doi:10.1016/S0092-8674(00)00126-4. ISSN 0092-8674. PMID 11057907.
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See also

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