Extending the nuclear roles of IκB kinase subunits

The transcription factor NF-kappa B plays a key role in a wide variety of cellular processes such as innate and adaptive immunity, cellular proliferation, apoptosis and development. In unstimulated cells, NF-kappa B is sequestered in the cytoplasm through its tight association with inhibitory proteins called I kappa BS, comprising notably I kappa B alpha. A key step in NF-kappa B activation is the phosphorylation Of I kappa B alpha by the so-called I kappa B kinase (IKK) complex, which targets the inhibitory protein for proteasomal degradation and allows the freed NF-kappa B to enter the nucleus where it can transactivate its target genes. The IKK complex is composed of two catalytic subunits called IKK alpha and IKK beta, and a regulatory subunit called NEMO/IKK gamma. Despite their key role in mediating I kappa B alpha phosphorylation in the cytoplasm, recent works have provided evidence that IKK subunits also translocate into the nucleus to regulate NF-kappa B-dependent and -independent gene expression, paving the way of a novel and exciting field of research. In this review, we will describe the current knowledge in that research area. (c) 2006 Elsevier Inc. All rights reserved.