Tuesday 9 January 2007
The p50 (NFKB1)/p65 (RELA) heterodimer is the most abundant form of NFKB.
The NFKB complex is inhibited by I-kappa-B proteins (NFKBIA) (MIM.164008) or NFKBIB (MIM.604495), which inactivate NFKB by trapping it in the cytoplasm.
Phosphorylation of serine residues on the I-kappa-B proteins by kinases IKBKA (MIM.600664) or IKBKB (MIM.603258) marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NFKB complex.
Activated NFKB complex translocates into the nucleus and binds DNA at kappa-B-binding motifs such as 5-prime GGGRNNYYCC 3-prime or 5-prime HGGARNYYCC 3-prime (where H is A, C, or T; R is an A or G purine; and Y is a C or T pyrimidine).
Gains or amplifications of the REL locus are frequently seen in primary mediastinal B-cell lymphoma (PMBL).
- gains/amplifications of REL in 75% of the PMBLs (17243160)
In classical Hodgkin’s lymphoma, genomic overrepresentation of REL correlated with nuclear REL protein accumulation.
Weniger MA, Gesk S, Ehrlich S, Martin-Subero JI, Dyer MJ, Siebert R, Moller P, Barth TF. Gains of REL in primary mediastinal B-cell lymphoma coincide with nuclear accumulation of REL protein. Genes Chromosomes Cancer. 2007 Apr;46(4):406-15. PMID: 17243160
Rodig SJ, Savage KJ, Lacasce AS, Weng AP, Harris NL, Shipp MA, Hsi ED, Gascoyne RD, Kutok JL. Expression of TRAF1 and Nuclear c-Rel Distinguishes Primary Mediastinal Large Cell Lymphoma From Other Types of Diffuse Large B-cell Lymphoma. Am J Surg Pathol. 2007 Jan;31(1):106-112. PMID: 17197926