NF-kappa-B/Rel/dorsal <p>Various studies (reviewed in [<cite idref="PUB00005235"/>, <cite idref="PUB00005385"/>, <cite idref="PUB00001009"/>, <cite idref="PUB00005520"/>, <cite idref="PUB00000840"/>]) have allowed the characterisation of afamily of eukaryotic transcription factors with basic impact on oncogenesis,embryonic development and differentiation including immune response and acutephase reaction. Members of this family include p50, p52, p65, c-Rel, v-Rrel, RelB, and the Drosophila proteins, Dorsal and Dif. Most of these transcription factors bind as homo- and heterodimers to theconsensus a DNA sequence motif termed kappa-B according thefirst described factor-binding sequence motif located in the immunoglobulinkappa light chain enhancer region.</p><p>Proteins of this family appear to be regulated, at least in part, bysubcellular localisation whereby the inactive cytoplasmic forms become activetranscriptional control proteins by translocation to the nucleus. Members ofthe Rel family share a highly conserved 300 amino acids domain termed Relhomology domain (RHD) located towards the amino terminus.For several proteins it has been demonstrated ([<cite idref="PUB00005235"/>] and references therein)that the Rel homology domain includes:<ol><li>a DNA-binding domain, which binds to the consensus DNA sequence motif 5'-GGGRNNYYCC-3' (except for dorsal, which recognises the related motif 5'-GRGAAAANCC-3');</li><li>a dimerisation domain, which is located in the C-terminal part of the RHD;</li><li>a PKA phosphorylation site (see <db_xref db="PROSITEDOC" dbkey="PDOC00004"/>) (except in RelB);</li><li>a nuclear localisation signal (NLS), which consists of a stretch of four or five basic residues.</li></ol></p><p>DNA binding requires the entire RHD, by contrast withother eukaryotic and prokaryotic transcription factors, where muchsmaller DNA-binding domains confer full specificity and bindingaffinity for the target [<cite idref="PUB00004200"/>]. The N-terminal region of the RHD includes a conserved cysteine that seems to be essential for DNA-binding in p50 [<cite idref="PUB00001846"/>]. The unique C-terminal(not found in p50 or p52) is thought to be involved in gene activation and cytoplasmic anchoring functions.</p><p>The structure of the transcription factor NF-kB p50 homodimer bound toa palindromic kB site shows the RHD to fold into 2 distinct domains,similar to the beta-sandwich structure of the immunoglobulins [<cite idref="PUB00004200"/>]. The p50 dimer envelops an undistorted B-DNA helix, making specific contactsalong the recognition site, mainly through loops connectingsecondary structure elements in both domains. The C-terminal domainsform a dimerisation interface between beta-sheets using residues thatare strongly conserved in the Rel family.</p>