Combinatorial mechanisms regulating AID-dependent DNA deamination: interacting proteins and post-translational modifications.
Combinatorial mechanisms regulating AID-dependent DNA deamination: interacting proteins and post-translational modifications.
复制标题
调节 AID 依赖性 DNA 脱氨作用的组合机制：相互作用的蛋白质和翻译后修饰。
DOI：
10.1016/j.smim.2012.05.006
复制
发表时间：
2012
影响因子：
7.8
通讯作者：
Chaudhuri,Jayanta
中科院分区：
文献类型：
--
作者：
Vuong,BaoQ;Chaudhuri,Jayanta
保护性体液免疫应答由免疫球蛋白（IG）多样化反应引起，该反应通过发育或成熟B细胞中的程序性DNA双链断裂和突变进行。初级IG多样性依赖于V（D）J重组和RAG蛋白，次级多样性通过类别转换重组（CSR）和体细胞超突变（SHM）实现，这需要AID（活化诱导的脱氨酶）。由于异常的AID活性可导致非IG基因座的突变和IG基因座与非IG基因之间的DNA易位，因此必须严格调控AID的活性。AID mRNA的表达受细胞因子刺激的转录调控，受miRNA的转录后调控。AID活性受翻译后修饰、亚细胞定位和与其他蛋白质相互作用的调节。所有这些分子机制都已进化为特异性诱导IG位点的AIDS依赖性突变和DNA双链断裂，以促进最大的IG基因多样化，同时限制该突变子进入非IG区域。
Protective humoral immune responses result from immunoglobulin (Ig) diversification reactions that proceed through programmed DNA double-strand breaks and mutations in developing or mature B cells. While primary Ig diversity is dependent on V(D)J recombination and the RAG proteins, secondary diversification is achieved through class switch recombination (CSR) and somatic hypermutation (SHM), which require AID (activation induced deaminase). Because aberrant AID activity can result in mutations in non-Ig loci and DNA translocations between the Ig locus and non-Ig genes, the activity of AID must be stringently regulated. AID mRNA expression is regulated transcriptionally by cytokine stimulation and post-transcriptionally by miRNAs. AID activity is regulated by post-translational modifications, subcellular localization, and interaction with other proteins. All of these molecular mechanisms have evolved to specifically induce AID-dependent mutations and DNA double-strand breaks at the Ig loci to promote maximal Ig gene diversification while limiting the access of this mutator to non-Ig regions.