IκB independent control of NF-κB activity by modulatory phosphorylations

Activation of the transcription factor nuclear factor kappaB (NF-kappaB) requires its release from inhibitor of NF-kappaB (I kappaB) proteins in the cytoplasm. Much work has focussed on the identification of pathways regulating this cytosolic rate-limiting step of NF-kappaB activation. However, there is increasing evidence for another complex level of NF-kappaB activation, which involves modulatory phosphorylations of the DNA-binding subunits. These phosphorylations can control several functions of NF-kappaB, including DNA binding and transactivation properties, as well as interactions between the transcription factor and regulatory proteins. Although their overall impact on NF-kappaB function has yet to be determined, modifications of this factor will very probably provide a mechanism to fine tune NF-kappaB function.