Extending the nuclear roles of IkappaB kinase subunits.

The transcription factor NF-kappaB 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-kappaB is sequestered in the cytoplasm through its tight association with inhibitory proteins called IkappaBs, comprising notably IkappaBalpha. A key step in NF-kappaB activation is the phosphorylation of IkappaBalpha by the so-called IkappaB kinase (IKK) complex, which targets the inhibitory protein for proteasomal degradation and allows the freed NF-kappaB to enter the nucleus where it can transactivate its target genes. The IKK complex is composed of two catalytic subunits called IKKalpha and IKKbeta, and a regulatory subunit called NEMO/IKKgamma. Despite their key role in mediating IkappaBalpha phosphorylation in the cytoplasm, recent works have provided evidence that IKK subunits also translocate into the nucleus to regulate NF-kappaB-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.