NF-κB Controls Expression of Inhibitor IκBα: Evidence for an Inducible Autoregulatory Pathway

The eukaryotic transcription factor nuclear factor-kappa B (NF-κB) participates in many parts of the genetic program mediating T lymphocyte activation and growth. Nuclear expression of NF-κB occurs after its induced dissociation from its cytoplasmic inhibitor IκBα. Phorbol ester and tumor necrosis factor-alpha induction of nuclear NF-κB is associated with both the degradation of performed IκBα and the activation of IκBα gene expression. Transfection studies indicate that the IκBα gene is specifically induced by the 65-kilodalton transactivating subunit of NF-κB. Association of the newly synthesized IκBα with p65 restores intracellular inhibition of NF-κB DNA binding activity and prolongs the survival of this labile inhibitor. Together, these results show that NF-κB controls the expression of IκBα by means of an inducible autoregulatory pathway.