IKBKE

Description

The IKBKE (inhibitor of nuclear factor kappa B kinase subunit epsilon) is a protein-coding gene located on chromosome 1.

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.

== Interactions == IKBKE has been shown to interact with TANK.

== Function == It is a 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 (TANK-binding kinase 1-binding protein 1) 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 (gamma-activation factor) (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.

IKBKE, also known as Inducible I kappa-B kinase, is a serine/threonine kinase that plays a crucial role in regulating inflammatory responses to viral infection. It activates the type I IFN, NF-kappa-B, and STAT signaling pathways. IKBKE is also involved in TNFA and inflammatory cytokine, like Interleukin-1, signaling. Upon activation of viral RNA sensors, such as RIG-I-like receptors, IKBKE associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This phosphorylation event enables homodimerization and nuclear translocation of IRF3, leading to transcriptional activation of pro-inflammatory and antiviral genes, including IFNB. To establish an antiviral state, IKBKE forms various complexes whose composition depends on the cell type and stimuli. Scaffolding molecules such as IPS1/MAVS, TANK, AZI2/NAP1, or TBKBP1/SINTBAD can be recruited to these IKBKE-containing complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, IKBKE regulates the NF-kappa-B signaling pathway by phosphorylating CYLD. IKBKE also phosphorylates inhibitors of NF-kappa-B, resulting in the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. IKBKE is required for the induction of a subset of ISGs that exhibit antiviral activity, possibly through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' promotes the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, regulating the balance between type I and type II IFN responses. IKBKE protects cells against DNA damage-induced cell death. It also plays a crucial role in energy balance regulation by sustaining chronic, low-grade inflammation in obesity, leading to a negative impact on insulin sensitivity. IKBKE phosphorylates AKT1. {ECO:0000269|PubMed:17568778, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:19153231, ECO:0000269|PubMed:20188669, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:22532683, ECO:0000269|PubMed:23453969, ECO:0000269|PubMed:23478265}

IKBKE is also known as IKK-E, IKK-i, IKKE, IKKI.

Associated Diseases

WES Whole Exome Sequencing