CHARACTERISTICS OF THE REL-HOMOLOGY DOMAIN

Various studies have allowed the characterization of a family of eukaryotic transcription factors with basic impact on oncogenesis, embryonic development and differentiation, including immune response and acute phase reaction. Most of these transcription factors bind as dimers to the consensus DNA sequence motif 5'-GGGRNNYYCC-3' termed kappa-B, according to the first described factor-binding sequence motif located in the immunoglobulin kappa light chain enhancer region.

Proteins of this family appear to be regulated, at least in part, by subcellular localization; the inactive cytoplasmic forms become active by translocation to the nucleus. Members of the Rel family share a highly conserved 300 amino acids domain termed Rel homology domain (RHD), which is located towards the amino terminus. The unique C-terminal is thought to be involved in gene activation and cytoplasmic anchoring functions.

Proteins known to contain a RHD domain are listed below:

• Both subunits of vertebrate nuclear factor NF-kappa-B (NFkB)
• Mammalian transcription factor RelB.
• Vertebrate proto-oncogene c-rel.
• Avian reticuloendotheliosis virus p58 v-rel.
• Drosophila embryonic polarity dorsal protein.
• Drosophila dorsal-related immunity factor.
• Mammalian nuclear factor of activated T cells (NFAT)

For several proteins it has been demonstrated that the Rel homology domain includes:

• A DNA-binding domain, which binds to the consensus DNA sequence motif 5'-GGGRNNYYCC-3' (except for dorsal, which recognizes the related motif 5'-GRGAAAANCC-3');
• A dimerization domain, which is located in the C-terminal part of the RHD;
• A PKA phosphorylation site (except in RelB);
• A nuclear localization signal (NLS), which consists of a stretch of four or five basic residues.