Activation-induced cytidine deaminase (AID) linking immunity, chronic inflammation, and cancer.
Activation-induced cytidine deaminase (AID) linking immunity, chronic inflammation, and cancer.
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DOI：
10.1007/s00262-012-1255-z
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发表时间：
2012-09
影响因子：
5.8
通讯作者：
Jensen-Jarolim, Erika
中科院分区：
文献类型：
--
作者：
Mechtcheriakova, Diana;Svoboda, Martin;Meshcheryakova, Anastasia;Jensen-Jarolim, Erika
关键词：
激活诱导的胞苷脱氨酶（AID）关键地参与类别转换重组和IG基因座的体细胞超突变，导致抗体库的多样化和高亲和力抗体的产生，并且因此代表引入DNA改变的生理工具。这些过程发生在次级淋巴器官的生发中心。在生理条件下，AID主要在活化的B淋巴细胞中表达。由于AID的致突变和重组潜力，其表达和活性在不同水平上受到严格调控，以最大限度地减少不必要的DNA损伤的风险。然而，慢性炎症和可能的其他尚未鉴定的因素的组合能够产生足以在B细胞中并且重要地在非B细胞背景中触发异常AID表达的微环境。在这些情况下，AID也可以靶向非Ig基因，包括癌症相关基因如癌基因、肿瘤抑制基因和基因组稳定性基因，并调节遗传和表观遗传信息。尽管正在取得进展，但仍然缺乏对基本方面的完全理解，如（1）触发异常AID表达/活性的关键因素是什么，包括Th 2驱动的炎症的影响，以及（2）人类非B细胞中异常AID在多大程度上可能导致与基因组改变（如点突变、小插入或缺失）的速率增加相关的异常细胞状态，和/或在实体瘤发展和进展期间的复发性染色体易位。
Activation-induced cytidine deaminase (AID) is critically involved in class switch recombination and somatic hypermutation of Ig loci resulting in diversification of antibodies repertoire and production of high-affinity antibodies and as such represents a physiological tool to introduce DNA alterations. These processes take place within germinal centers of secondary lymphoid organs. Under physiological conditions, AID is expressed predominantly in activated B lymphocytes. Because of the mutagenic and recombinogenic potential of AID, its expression and activity is tightly regulated on different levels to minimize the risk of unwanted DNA damage. However, chronic inflammation and, probably, combination of other not-yet-identified factors are able to create a microenvironment sufficient for triggering an aberrant AID expression in B cells and, importantly, in non-B-cell background. Under these circumstances, AID may target also non-Ig genes, including cancer-related genes as oncogenes, tumor suppressor genes, and genomic stability genes, and modulate both genetic and epigenetic information. Despite ongoing progress, the complete understanding of fundamental aspects is still lacking as (1) what are the crucial factors triggering an aberrant AID expression/activity including the impact of Th2-driven inflammation and (2) to what extent may aberrant AID in human non-B cells lead to abnormal cell state associated with an increased rate of genomic alterations as point mutations, small insertions or deletions, and/or recurrent chromosomal translocations during solid tumor development and progression.
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影响因子：
8
作者：
Endo, Y.;Marusawa, H.;Chiba, T.
通讯作者：
Chiba, T.
DOI：
10.1073/pnas.0708220105
发表时间：
2008-01-29
影响因子：
11.1
作者：
Hauser, Jannek;Sveshnikova, Natalia;Grundstrom, Thomas
通讯作者：
Grundstrom, Thomas
DOI：
10.1084/jem.20081319
发表时间：
2008-10-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
McBride KM;Gazumyan A;Woo EM;Schwickert TA;Chait BT;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
4.8
作者：
Brar, SS;Watson, M;Diaz, M
通讯作者：
Diaz, M
影响因子：
4.8
作者：
Chen, Zhengshan;Gu, Jiang
通讯作者：
Gu, Jiang