IκB: a Specific Inhibitor of the NF-κB Transcription Factor

TLDR

NF‑κB is normally cytosolic and binds DNA only when a dissociating agent such as sodium deoxycholate is present. Phorbol ester activates protein kinase C, which modifies IκB and dissociates the NF‑κB/IκB complex. The study identifies a 60–70 kDa inhibitor, IκB, that binds NF‑κB in the cytoplasm, blocks its DNA binding, and is released by phorbol ester‑induced protein kinase C activity, allowing NF‑κB to enter the nucleus.

Abstract

In cells that do not express immunoglobulin kappa light chain genes, the kappa enhancer binding protein NF-κB is found in cytosolic fractions and exhibits DNA binding activity only in the presence of a dissociating agent such as sodium deoxycholate. The dependence on deoxycholate is shown to result from association of NF-κB with a 60- to 70-kilodalton inhibitory protein (IκB). The fractionated inhibitor can inactivate NF-κB from various sources—including the nuclei of phorbol ester-treated cells—in a specific, saturable, and reversible manner. The cytoplasmic localization of the complex of NF-κB and IκB was supported by enucleation experiments. An active phorbol ester must therefore, presumably by activation of protein kinase C, cause dissociation of a cytoplasmic complex of NF-κB and IκB by modifying IκB. This releases active NF-κB which can translocate into the nucleus to activate target enhancers. The data show the existence of a phorbol ester-responsive regulatory protein that acts by controlling the DNA binding activity and subcellular localization of a transcription factor.