REL gene

The REL gene (REL stands for: REL Proto-Oncogene, NF-KB Subunit) and is a protein-coding gene located on chromosome 2p16.1.

REL is a protooncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor that is present in almost all cell types and is involved in many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis, and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL, and NFKB2/p52. The dimers bind to kappa B sites in the DNA of their target genes . The individual dimers have different preferences for different kappa B sites to which they can bind with distinguishable affinity and specificity.

Different dimer combinations act as transcriptional activators or repressors. NF-kappa-B is controlled by various mechanisms of posttranslational modification and subcellular compartmentalization, as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are maintained in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor family (I-kappa-B). In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to various activators and subsequently degraded, releasing the active NF-kappa-B complex, which translocates to the nucleus. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator.

REL-related diseases include immunodeficiency 92 and reticuloendotheliosis. Related signaling pathways include immune response (NFAT) and IL-1 family signaling pathways. An important paralog of this gene is RELA.

Psoriasis: Evidence is accumulating that the REL gene, as a member of the NF-κB family, is a risk factor for psoriasis. When REL is inactivated, the expression of cytokine IL-23 (a direct target of c-Rel), which can drive the development of IL-17-producing T cells, is significantly inhibited. Potentially, this may provide therapeutic approaches.

1. Fan T et al. (2016) Treating psoriasis by targeting its susceptibility gene Rel. Clin Immunol 165:47-54.
2. Wulczyn FG et al. (1996) The NF-kappa B/Rel and I kappa B gene families: mediators of immune response and inflammation. J Mol Med (Berl) 74:749-769.