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Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Mini Review RELA (v-rel reticuloendotheliosis viral oncogene homolog A) Fei Chen Health Effects Laboratory Division, NIOSH, 1095 Willowdale Rd, Morgantown, WV 26505, USA (FC) Published in Atlas Database: January 2002 Online updated version: http://AtlasGeneticsOncology.org/Genes/RELAID325.html DOI: 10.4267/2042/37835 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2002 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Protein Other names: NF-kB3; NF-kB p65 HGNC (Hugo): RELA Location: 11q12-q13 Description The relA gene encodes a protein composed 551 amino acids with an approximately molecular weight of 65 kDa. The N-terminal region of RelA contains a Rel homology domain (RHD) followed by a nuclear localization signal. The C-terminal region of RelA contains a putative leucine zipper domain and a transactivation domain that is important for the NF-kBmediated gene transactivation. A number of protein kinases can phosphorylate RelA and consequently potentiate the transcriptional activity of NF-kB complexes. These kinases include IKKb, PKA, and possibly GSK3 and MAP kinase p38. The phosphorylation of the transactivation domain of RelA was considered as an important event for the recruitment and/or interaction with co-factors and general transcriptional machinery subunits such as p300 and TFIIB. Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Note See also, in the Deep Insight section: Upstream Signal Transduction of NF-kB Activation DNA/RNA Expression Description Wide. The gene encoding human RelA has 10 exons spanning 8.1 kb. The shorter variants of RelA (p65d) can be generated by alternative splicing of intron 1, 6, or 7. The p65d1 lacks codons for amino acids 222 to 231 and p65d2 lacks codons for amino acids 13 to 25 of the conserved Rel homology domain. An additional alternative splicing form of p65, p65d3 has been identified in a non-small-cell lung carcinoma cell line that lacks codons for amino acids 187 to 293 of the Rel homology domain. Atlas Genet Cytogenet Oncol Haematol. 2002; 6(2) Localisation Cytosol, nuclei after activation. Function regulation of the genes involved in cell-to-cell interaction, intercellular communication, cell recruitment or transmigration, amplification or spreading of primary pathogenic signals, 100 RELA Chen F cell apoptosis, and initiation or acceleration of tumorigenesis. The p50/RelA complex is the most abundant NF-kB complex in all type tissues or cells. Interaction with: members of IkB family and Rel family; GR; HDAC3; CREB; p300; Sp1, Egr1; AES; TFIIB. References Van Den Berghe H, Parloir C, David G, Michaux JL, Sokal G. A new characteristic karyotypic anomaly in lymphoproliferative disorders. Cancer. 1979 Jul;44(1):188-95 Deloukas P, van Loon AP. Genomic organization of the gene encoding the p65 subunit of NF-kappa B: multiple variants of the p65 protein may be generated by alternative splicing. Hum Mol Genet. 1993 Nov;2(11):1895-900 Implicated in Cancer, autoimmune arthritis, glomerulonephritis, asthma, inflammatory bowel disease, septic shock, lung fibrosis, HTLV-1 infection, and AIDS Baldwin AS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649-83 Ghosh S, May MJ, Kopp EB. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225-60 Zhong H, Voll RE, Ghosh S. Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol Cell. 1998 Apr;1(5):661-71 Oncogenesis Chromosomal rearrangement or point mutation of relA gene has been implicated infrequently in human lymphoid tumors. A t(11;14)(q14;q32?) chromosomal translocation was described in 4 cases of lymphoproliferative disorders (LPD), which possibly involved p65 gene rearrangement. Gene amplification or increased expression of relA has also been noted in some cases of squamous carcinomas of head and neck, and in adenocarcinomas of breast and stomach. Atlas Genet Cytogenet Oncol Haematol. 2002; 6(2) Rayet B, Gélinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene. 1999 Nov 22;18(49):6938-47 This article should be referenced as such: Chen F. RELA (v-rel reticuloendotheliosis viral oncogene homolog A). Atlas Genet Cytogenet Oncol Haematol. 2002; 6(2):100-101. 101