NF-KAPPA-B CONTROLS EXPRESSION OF INHIBITOR I-KAPPA-B-ALPHA - EVIDENCE FOR AN INDUCIBLE AUTOREGULATORY PATHWAY

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