AUTOREGULATION OF I-KAPPA-B-ALPHA ACTIVITY

Transcription factor NF-kappaB regulates the expression of a plethora of genes. The activity of NF-kappaB proteins is regulated by IkappaB p roteins. We report that induction of IkappaBalpha, a member of the Ika ppaB family of proteins, is preceded by activation of NF-kappaB comple x. The promoter of the IkappaBalpha gene contains a kappaB site that i s directly involved in its induction by the NF-kappaB complex. Degrada tion of IkappaBalpha protein precedes activation of NF-kappaB DNA bind ing activity, whereas newly synthesized IkappaBalpha protein inhibits NF-kappaB activity. If the degradation of IkappaBalpha is prevented, t he induction of DNA binding activity of NF-kappaB complex is severely curtailed. These data suggest the existence of an autoregulatory loop whereby IkappaBalpha regulates the activity of transcription factor NF -kappaB, which in turn regulates the IkappaBalpha activity.