Calmodulin dependence of NFκB activation

The NFκB family of transcription factors is regulated by inhibitory IκB proteins. A diversity of stimuli leads to the phosphorylation and subsequent degradation of IκB, releasing NFκB to act on its target genes. Calmodulin (CaM) is a key regulator of numerous cellular processes and is the predominant intracellular receptor for Ca 2+ signals. Here we report that several CaM antagonists inhibit the activation of NFκB, and that this is due to the prevention of inducible IκB phosphorylation. Our results suggest that CaM is involved in the phosphorylation of IκB, a finding that may help in elucidating the mechanism of this critical step of NFκB activation.