活化诱导胞苷脱氨酶的翻译后调控
Post-translational regulation of activation-induced cytidine deaminase.
作者信息
Basu Uttiya, Franklin Andrew, Alt Frederick W
机构信息
Howard Hughes Medical Institute, The Children's Hospital, Boston, MA 02115, USA.
出版信息
Philos Trans R Soc Lond B Biol Sci. 2009 Mar 12;364(1517):667-73. doi: 10.1098/rstb.2008.0194.
Abstract
The assembled immunoglobulin genes in the B cells of mice and humans are altered by distinct processes known as class switch recombination (CSR) and somatic hypermutation, leading to diversification of the antibody repertoire. These two DNA modification processes are initiated by the B cell-specific protein factor activation-induced cytidine deaminase (AID). AID is post-translationally modified by phosphorylation at multiple sites, although functional significance during CSR has been implicated only for phosphorylation at serine-38 (S38). Although multiple laboratories have demonstrated that AID function is regulated via phosphorylation at S38, the precise biological role of S38 phosphorylation has been a topic of debate. Here, we discuss our interpretation of the significance of AID regulation via phosphorylation and also discuss how this form of AID regulation may have evolved in higher organisms.
摘要
小鼠和人类B细胞中组装好的免疫球蛋白基因会通过称为类别转换重组（CSR）和体细胞超突变的不同过程发生改变，从而导致抗体库的多样化。这两种DNA修饰过程由B细胞特异性蛋白因子激活诱导的胞苷脱氨酶（AID）启动。AID在多个位点被磷酸化进行翻译后修饰，尽管在CSR过程中的功能意义仅涉及丝氨酸38（S38）的磷酸化。虽然多个实验室已证明AID功能通过S38磷酸化进行调节，但S38磷酸化的确切生物学作用一直是一个争论的话题。在这里，我们讨论我们对通过磷酸化调节AID的意义的解读，并且还讨论这种AID调节形式可能是如何在高等生物中进化的。
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