Regulation of DNA binding by Rel/NF-κB transcription factors: structural views

Rel/NF-κB transcription factors form homo- and heterodimers with different DNA binding site specificities and DNA binding affinities. Several intracellular pathways evoked by a wide range of biological factors and environmental conditions can lead to the activation of Rel/NF-κB dimers by signaling degradation of the inhibitory IκB protein. In the nucleus Rel/NF-κB dimers modulate the expression of a variety of genes including those encoding cytokines, growth factors, acute phase response proteins, immunoreceptors, other transcription factors, cell adhesion molecules, viral proteins and regulators of apoptosis. The primary focus of this review is on structural and functional aspects of Rel/NF-κB:DNA complexes and their formation. The salient features of the Rel/NF-κB dimer:DNA structure are described, as are modes of transcriptional regulation by phosphorylation, altered DNA binding properties, varying protein conformations, and interactions with IκB proteins.

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