Specification of DNA binding activity of NF-kappaB proteins

Nuclear factor-kappaB (NF-kappaB) is a pleiotropic mediator of inducible and specific gene regulation involving diverse biological activities including immune response, inflammation, cell proliferation, and death. The fine-tuning of the NF-kappaB DNA binding activity is essential for its fundamental function as a transcription factor. An increasing body of literature illustrates that this process can be elegantly and specifically controlled at multiple levels by different protein subsets. In particular, the recent identification of a non-Rel subunit of NF-kappaB itself provides a new way to understand the selective high-affinity DNA binding specificity of NF-kappaB conferred by a synergistic interaction within the whole complex. Here, we review the mechanism of the specification of DNA binding activity of NF-kappaB complexes, one of the most important aspects of NF-kappaB transcriptional control.