Role of Unphosphorylated, Newly Synthesized IκBβ in Persistent Activation of NF-κB

Abstract

Stimulation with inducers that cause persistent activation of NF-κB results in the degradation of the NF-κB inhibitors, IκBα and IκBβ. Despite the rapid resynthesis and accumulation of IκBα, NF-κB remains induced under these conditions. We now report that IκBβ is also resynthesized in stimulated cells and appears as an unphosphorylated protein. The unphosphorylated IκBβ forms a stable complex with NF-κB in the cytosol; however, this binding fails to mask the nuclear localization signal and DNA binding domain on NF-κB, and the IκBβ–NF-κB complex enters the nucleus. It appears therefore that during prolonged stimulation, IκBβ functions as a chaperone for NF-κB by protecting it from IκBα and allowing it to be transported to the nucleus.