ROLE OF UNPHOSPHORYLATED, NEWLY SYNTHESIZED I-KAPPA-B-BETA IN PERSISTENT ACTIVATION OF NF-KAPPA-B

Stimulation with inducers that cause persistent activation of NF-kappa B results in the degradation of the NF-kappa E inhibitors, I kappa B alpha and I kappa B beta. Despite the rapid resynthesis and accumulati on of I kappa B alpha, NF-kappa B remains induced under these conditio ns, We now report that I kappa B beta is also resynthesized in stimula ted cells and appears as an unphosphorylated protein, The unphosphoryl ated I kappa B beta forms a stable complex with NF-kappa B in the cyto sol; however, this binding fails to mask the nuclear localization sign al acid DNA binding domain on NF-KIC, and the I kappa B beta-NF-kappa B complex enters the nucleus. It appears therefore that during prolong ed stimulation, I kappa B beta functions as a chaperone for NF-kappa B by protecting it from I kappa B alpha and allowing it to be transport ed to the nucleus.