IKK2

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Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta
Protein IKBKB PDB 3BRT.png
Rendering based on PDB 3BRT.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols IKBKB ; IKK-beta; IKK2; IKKB; IMD15; NFKBIKB
External IDs OMIM603258 MGI1338071 HomoloGene7782 ChEMBL: 1991 GeneCards: IKBKB Gene
EC number 2.7.11.10
RNA expression pattern
PBB GE IKBKB 209341 s at tn.png
PBB GE IKBKB 209342 s at tn.png
PBB GE IKBKB 211027 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3551 16150
Ensembl ENSG00000104365 ENSMUSG00000031537
UniProt O14920 O88351
RefSeq (mRNA) NM_001190720 NM_001159774
RefSeq (protein) NP_001177649 NP_001153246
Location (UCSC) Chr 8:
42.13 – 42.19 Mb
Chr 8:
22.66 – 22.71 Mb
PubMed search [1] [2]

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[edit]

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[edit]

IKK-β plays a significant role in brain cells following a stroke.[citation needed] 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.[1]

Inhibition of IKK and IKK-related kinases has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer.[2] The small-molecule inhibitor of IKK2 SAR113945, developed by Sanofi-Aventis, was evaluated in patients with knee osteoarthritis.[2][3]

Model organisms[edit]

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.[4] Additionally, experimental mice with an overactive form of IKK-β experience loss of many more neurons than normal mice after a stroke-simulating event.[1] Researchers found a molecule that could block the signaling of IKK-β for up to four and a half hours.[5] 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.[6]

A conditional knockout mouse line, called Ikbkbtm1a(EUCOMM)Wtsi[11][12] 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.[13][14][15]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] 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.[9]

Interactions[edit]

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

References[edit]

  1. ^ a b BBC News. 14 November 2005. Stroke 'cell-death trigger' found. Retrieved on June 28, 2007.
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  3. ^ "SAR113945 published clinical trials". 
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  5. ^ Herrmann, O; Baumann, B; De Lorenzi, R; Muhammad, S; Zhang, W; Kleesiek, J; Malfertheiner, M; Köhrmann, M et al. (2005). "IKK mediates ischemia-induced neuronal death". Nature Medicine 11 (12): 1322–9. doi:10.1038/nm1323. PMID 16286924. 
  6. ^ Heckmann A, Waltzinger C, Jolicoeur P, Dreano M, Kosco-Vilbois MH, and Sagot Y. 2004. IKK-β Inhibitor Alleviates Kidney and Wasting Diseases in a Murine Model of Human AIDS. American Journal of Pathology. Volume 164, Pages 1253-1262. Retrieved on June 30, 2007.
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See also[edit]