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

TLDR

The eukaryotic transcription factor NF‑κB is a key regulator of T‑cell activation and growth. Transfection experiments reveal that NF‑κB p65 directly induces the IκBα gene, and the newly synthesized IκBα binds p65 to re‑inhibit NF‑κB DNA binding and prolong IκBα stability. The data show that NF‑κB activation simultaneously promotes IκBα gene expression and degrades existing IκBα, establishing an inducible autoregulatory loop that restores NF‑κB inhibition.

Abstract

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