IKK biology

Abstract

Summary The inhibitor of nuclear factor-κB (IκB) kinase (IKK) complex is the master regulator of the NF-κB signaling pathway. The activation of the IKK complex is a tightly regulated, highly stimulus-specific, and target-specific event that is essential for the plethora of functions attributed to NF-κB. More recently, NF-κB independent roles of IKK members have brought increased complexity to its biological function. This review highlights some of the major advances in the studies of the process of IKK activation and the biological roles of IKK family members, with a focus on NF-κB independent functions. Understanding these complex processes is essential for targeting IKK for therapeutics.

Protein Tyrosine Phosphatase with Proline-Glutamine-Serine-Threonine–Rich Motifs Negatively Regulates TLR-Triggered Innate Responses by Selectively Inhibiting IκB Kinase β/NF-κB Activation

“…The IKK complex is able to phosphorylate IkBa and leads to the degradation of IkBa. IKK activation has been proposed to depend on phosphorylation of IKKb at Ser 177/181 on its activation loop, which might in turn induce the complex conformation change and exposure of kinase domain (37,45). In the current study, PTP-PEST directly associates with IKKb.…”

Integration of Apoptosis Signal-Regulating Kinase 1-Mediated Stress Signaling with the Akt/Protein Kinase B-IκB Kinase Cascade

“…Notably, Akt activates the prominent prosurvival kinase, IKK (14)(15)(16). Although IKK plays a vital role in NF-B activation, the importance of IKK in the regulation of other signaling events is becoming increasingly evident (17). Thus, we tested the premise that IKK phosphorylates ASK1.…”

Histone Deacetylase (HDAC) Inhibition Induces IκB Kinase (IKK)-dependent Interleukin-8/CXCL8 Expression in Ovarian Cancer Cells

“…At the transcriptional level, IL-8/CXCL8 expression is regulated by the transcription factor NFB, which is constitutively activated in ovarian cancer (OC) cells and conveys a poor outcome (3)(4)(5). Activation of NFB is mediated by the enzymes of the IB kinase (IKK) complex, which, in addition to phosphorylating IB␣, leading to its proteasomal degradation, can phosphorylate NFB subunits and other transcription factors and cofactors (6,7). Although the proteasomal degradation of IB␣, resulting in the nuclear accumulation of NFB subunits, represents a general step in NFB activation, the specificity and duration of NFB-regulated responses are mediated by the protein composition of NFB complexes and their posttranslational modifications (8 -11).…”