Activation-induced cytidine deaminase auto-activates and triggers aberrant gene expression
Activation-induced cytidine deaminase auto-activates and triggers aberrant gene expression
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DOI：
10.1016/j.febslet.2013.06.028
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发表时间：
2013-08-19
期刊：
影响因子：
3.5
通讯作者：
Yoshizaki, Kazuyuki
中科院分区：
文献类型：
--
作者：
Isobe, Tomoyasu;Song, Soken-Nakazawa J.;Yoshizaki, Kazuyuki
DNA甲基化是一个表征良好的表观遗传里程碑，涉及转录调控；然而，其调控机制仍不清楚。近年来的研究表明，激活诱导胞苷脱氨酶（AID）参与了活性DNA去甲基化。AID在炎症相关癌症中异常表达并产生点突变；然而，归因于其去甲基化功能的细胞疾病在很大程度上尚未被探索。本研究表明异位AID表达会干扰肿瘤相关基因的表达。AID（与Gadd45一起）激活了一个甲基化的配对盒基因5 （Pax5）报告基因构建体，诱导内源性Pax5与AID启动子的表达和关联，表明AID异常表达触发了一个自激活回路以巩固自我表达。蛋白质相互作用的结构化总结：AID通过抗标签共免疫沉淀与GADD45 α物理相互作用（View Interaction: 1,2,3） (C) 2013 Federation of European Biochemical Societies。Elsevier B.V.版权所有。
DNA methylation is a well-characterized epigenetic landmark involved in transcriptional regulation; however, mechanisms underlying its regulation remain poorly characterized. Recent studies demonstrate that activation-induced cytidine deaminase (AID) is involved in active DNA demethylation. AID is aberrantly expressed in inflammation-associated cancers and generates point mutations; however, cellular disorders attributed to its demethylation function are largely unexplored. Here we demonstrate that ectopic AID expression perturbs tumor-related gene expression. AID (with Gadd45) activated a methylated paired box gene 5 (Pax5) reporter construct, and induced expression and association of endogenous Pax5 with the AID promoter, suggesting that aberrant AID expression triggers an auto-activation circuit to consolidate self-expression.Structured summary of protein interactions:AID physically interacts with GADD45 alpha by anti tag coimmunoprecipitation (View Interaction: 1, 2, 3) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.