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首页> 外文期刊>Molecular and Cellular Biology >Amino-Terminal Phosphorylation of Activation-Induced Cytidine Deaminase Suppresses c-myc/IgH Translocation
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Amino-Terminal Phosphorylation of Activation-Induced Cytidine Deaminase Suppresses c-myc/IgH Translocation

机译：激活诱导的胞苷脱氨酶的氨基末端磷酸化抑制c-myc / IgH易位。

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Activation-induced cytidine deaminase (AID) is a mutator enzyme that initiates class switch recombination and somatic hypermutation of immunoglobulin genes (Ig) in B lymphocytes. However, AID also produces off-target DNA damage, including mutations in oncogenes and double-stranded breaks that can serve as substrates for oncogenic chromosomal translocations. AID is strictly regulated by a number of mechanisms, including phosphorylation at serine 38 and threonine 140, which increase activity. Here we show that phosphorylation can also suppress AID activity in vivo. Serine 3 is a novel phospho-acceptor which, when mutated to alanine, leads to increased class switching and c-myc/IgH translocations without affecting AID levels or catalytic activity. Conversely, increasing AID phosphorylation specifically on serine 3 by interfering with serine/threonine protein phosphatase 2A (PP2A) leads to decreased class switching. We conclude that AID activity and its oncogenic potential can be downregulated by phosphorylation of serine 3 and that this process is controlled by PP2A.
机译：激活诱导的胞苷脱氨酶（AID）是一种突变酶，可启动B淋巴细胞中免疫球蛋白基因（ Ig ）的类别转换重组和体细胞超突变。但是，AID也会产生脱靶DNA损伤，包括致癌基因突变和双链断裂，可作为致癌染色体易位的底物。 AID受到多种机制的严格调控，包括增加活性的丝氨酸38和苏氨酸140的磷酸化。在这里，我们证明磷酸化还可以抑制体内的AID活性。丝氨酸3是一种新型的磷酸受体，当突变为丙氨酸时，会导致类别转换和c- myc / IgH易位增加，而不会影响AID水平或催化活性。相反，通过干扰丝氨酸/苏氨酸蛋白磷酸酶2A（PP2A）来提高AID在丝氨酸3上的磷酸化，会导致类别转换降低。我们得出的结论是，AID活性及其致癌潜力可通过丝氨酸3的磷酸化而下调，并且该过程受PP2A控制。

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