IKBKE

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IKBKE
Identifiers
Aliases IKBKE, IKK-E, IKK-i, IKKE, IKKI, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon, inhibitor of nuclear factor kappa B kinase subunit epsilon
External IDs MGI: 1929612 HomoloGene: 23168 GeneCards: IKBKE
Gene location (Human)
Chromosome 1 (human)
Chr. Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for IKBKE
Genomic location for IKBKE
Band No data available Start 206,470,476 bp[1]
End 206,496,889 bp[1]
RNA expression pattern
PBB GE IKBKE 204549 at fs.png

PBB GE IKBKE 214398 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001193321
NM_001193322
NM_014002

NM_019777

RefSeq (protein)

NP_001180250
NP_001180251
NP_054721

NP_062751

Location (UCSC) Chr 1: 206.47 – 206.5 Mb Chr 1: 131.25 – 131.28 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Inhibitor of nuclear factor kappa-B kinase subunit epsilon also known as I-kappa-B kinase epsilon or IKK-epsilon is an enzyme that in humans is encoded by the IKBKE gene.[5][6][7]

Interactions[edit]

IKBKE has been shown to interact with TANK.[8]

Function[edit]

Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, which leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.[9]

Clinical significance[edit]

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.[10]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000263528 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042349 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Shimada T, Kawai T, Takeda K, Matsumoto M, Inoue J, Tatsumi Y, Kanamaru A, Akira S (September 1999). "IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases". Int Immunol. 11 (8): 1357–62. PMID 10421793. doi:10.1093/intimm/11.8.1357. 
  6. ^ Peters RT, Liao SM, Maniatis T (July 2000). "IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex". Mol Cell. 5 (3): 513–22. PMID 10882136. doi:10.1016/S1097-2765(00)80445-1. 
  7. ^ "Entrez Gene: IKBKE inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon". 
  8. ^ Nomura F, Kawai T, Nakanishi K, Akira S (March 2000). "NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation". Genes Cells. 5 (3): 191–202. PMID 10759890. doi:10.1046/j.1365-2443.2000.00315.x. 
  9. ^ "Inhibitor of nuclear factor kappa-B kinase subunit epsilon". 
  10. ^ 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. PMID 24237125. doi:10.4155/ppa.13.31. 

Further reading[edit]