%0 Journal Article
%T The role of A20 in the pathogenesis of lymphocytic malignancy
%A Fan Zhang
%A Lijiang Yang
%A Yangqiu Li
%J Cancer Cell International
%D 2012
%I BioMed Central
%R 10.1186/1475-2867-12-44
%X Autoimmune phenomena were identified in many different cases of hematological diseases and solid tumors in which abnormal A20 expression was characterized. Recently, a number of studies have shown that A20 deletions and mutations are frequently found in lymphomas, suggesting that it may be involved in pathogenesis [1].A20 is also known as tumor necrosis factor-¦Á (TNF¦Á)-induced protein 3 (TNFAIP3), which was first discovered in 1990 by Dixit and colleagues as a cytokine-induced gene in human umbilical vein endothelial cells [2,3]. This protein was originally identified as a key regulator of inflammation signaling pathways and a negative regulator of the nuclear factor kappa B (NF-¦ÊB) activation pathway, which could attenuate the NF-¦ÊB activity triggered by signaling from several surface receptors including tumor necrosis factors receptor (TNFR), Toll-like receptor (TLR), and B cell receptor (BCR) [4].The A20 gene is located on chromosome 6q23.3, and the cDNA sequence is 4,440 bp long with an open reading frame of 2,370 nucleotides that encodes a protein predicted to contain 790 amino acids. A20 contains seven zinc finger (ZnF) domains in its C-terminus including one that functions as an E3 ligase, while an OUT (ovarian tumor) domain is embedded in its N-terminus [2,3,5-9]. Structural studies have revealed that the fourth zinc finger (ZnF4) interacts with mono-ubiquitins and K63-linked polyubiquitin chains [9].A20 expression may be induced in multiple organs by various stimuli including interleukin-1¦Â(IL-1¦Â), TNF-¦Á, and Epstein-Barr virus (EBV) - latent membrane protein1(LMP1). Although A20 is inducible by proinflammatory cytokines in most cell types, the regulation of A20 differs in lymphocytes. Temporally restricted and tissue-specific A20 expression patterns were observed with strikingly high levels in lymphoid organs including the thymus, spleen, and gut-associated lymphoid tissue. A20 is constitutively expressed in immature and mature thymocyte subpopulations and
%K A20 (TNFAIP3)
%K NF-¦ÊB
%K Tumor suppressor
%K Lymphocytic malignancy
%U http://www.cancerci.com/content/12/1/44