Proteins that bind to IKKgamma (NEMO) and down-regulate the activation of NF-kappaB

Abstract

Inhibitor of kappaB kinase (IKK) gamma (IKKgamma), also referred to as nuclear factor kappaB (NF-kappaB) essential modulator (NEMO), is an important component of the IKK complex. Following the exposure of cells to NF-kappaB-inducing stimuli, the IKK complex catalyzes the phosphorylation of inhibitor of kappaB (IkappaB) proteins, which is a critical step that leads to the activation of NF-kappaB via the canonical pathway. The exact functions of IKKgamma as part of the IKK complex have not been fully elucidated. A number of proteins have been identified as directly interacting with IKKgamma and modulating the activity of the IKK complex. This mini review covers eight proteins that have been reported to bind to IKKgamma and lead to the suppression of the activities of the IKK complex and hence result in the down-regulation of the activation of NF-kappaB. The reported mechanisms by which these interactions suppress the activation of the IKK complex include the deubiquitination of IKKgamma and competition with upstream activators for binding to IKKgamma.