IkappaB kinase epsilon interacts with p52 and promotes transactivation via p65

Abstract

The members of the NF-?B transcription factor family are key regulators of gene expression in the immune response. Different combinations of NF-?B subunits not only diverge in timing to induce transcription but also recognize varying sequences of the NF-?B-binding site of their target genes. The p52 subunit is generated as a result of processing of NF-?B2 p100. Here, we demonstrate that the non-canonical I?B kinase ? (IKK?) directly interacts with p100. In a transactivation assay, IKK? promoted the ability of p52 to transactivate gene expression. This effect was indirect, requiring p65, which was shown to be part of the IKK?-p52 complex and to be phosphorylated by IKK?. These novel interactions reveal a hitherto unknown function of IKK? in the regulation of the alternative NF-?B activation pathway involving p52 and p65.