Protein–protein interactions involving IKKγ (NEMO) that promote the activation of NF‐κB

Abstract

Inhibitor of kappaB kinase (IKK) gamma (IKKgamma), also referred to as nuclear factor kappaB (NF-kappaB) essential modulator (NEMO), is an important regulatory component of the IKK complex. The IKK complex is a signalosome that catalyzes the inducible phosphorylation of IkappaB proteins, which is a key step that leads to the activation of NF-kappaB. The exact functions of IKKgamma (NEMO) as part of the IKK complex have not yet been fully elucidated. This mini-review covers 16 proteins that have been reported to bind to IKKgamma and lead to the enhancement of the activities of the IKK complex, thus resulting in NF-kappaB activation. The major mechanisms by which these interactions are mediated involve the recognition of ubiquitinated upstream signaling components by IKKgamma or the modification of IKKgamma itself by ubiquitination. Additional mechanisms include the sumoylation or phosphorylation of IKKgamma and the modification of the tertiary or quaternary structure of IKKgamma.

IκB Kinase γ/Nuclear Factor-κB-Essential Modulator (IKKγ/NEMO) Facilitates RhoA GTPase Activation, which, in Turn, Activates Rho-associated Kinase (ROCK) to Phosphorylate IKKβ in Response to Transforming Growth Factor (TGF)-β1

“…RhoA-RhoGDI Complex Binds to IKK␥ Allowing RhoA Activation-Generally, IKK␥ provides binding sites for many proteins; 16 proteins have been reported as directly binding to IKK␥ and promoting the activation of NF-B (38). Here, we presented that RhoA-GDP and RhoGDI are also bound to IKK␥; RhoA-GDP was bound to the N-terminal domain (aa and RhoGDI was bound to the large C-terminal domain (estimated aa 112-419) of IKK␥.…”

NF-κB Essential Modulator (NEMO) Is Critical for Thyroid Function

“…This pathway seems to be independent of NEMO activity (1). Recent publications have also shown that diverse posttranslational modifications, including ubiquitination, sumoylation, and phosphorylation, regulate the function of NEMO in the IKK complex (2)(3)(4)(5)(6).…”

“…Two distinct pathways of NF-B activation have been reported. The classical, canonical pathway is found in virtually all mammalian cells and depends on the presence of the IKK␥/NF-B essential modulator (NEMO) 3 protein (1). In this pathway, NF-B activation is mediated by the IKK complex, consisting of the IKK1/IKK␣ and IKK2/IKK␤ catalytic kinase subunits and the NEMO regulatory protein (1).…”

Wogonoside alleviates inflammation induced by traumatic spinal cord injury by suppressing NF-κB and NLRP3 inflammasome activation

“…NF-κB is a multi-functional nuclear transcription factor, and is associated with the LPS-induced inflammatory response (19). In the cytoplasm, IκB binds with inactive NF-κB, which covers the nuclear localization sequence of NF-κB and thus prevents the activation and nuclear translocation of NF-κB (20). IκB degradation is therefore required for the activation of NF-κB.…”