National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.
J Leukoc Biol. 2018 Mar;103(3):433-444. doi: 10.1002/JLB.2MR0717-310R. Epub 2017 Dec 15.
The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytosine deaminases plays crucial roles in innate immunity through the ability of restricting viral replication by deamination and mutation of viral genomes. The antiviral function of these proteins was first discovered when research in the field of HIV infection revealed that one member of the family, namely APOBEC3G, restricts HIV infection in T lymphocytes and that the viral infectivity factor protein drives the proteosomal degradation of this enzyme, thus overriding its antiviral function. Recent advances in cancer genomics, together with biochemical characterization of the APOBEC3 enzymes, have now implicated some family members in somatic mutagenesis during carcinogenesis. While several studies investigated the downstream consequences of APOBEC3 expression and activity, either in the context of viral infection or tumorigenesis, little is known on the upstream mechanisms regulating APOBEC3 expression. Such knowledge would be of huge importance in developing innovative approaches to strengthen antiviral innate immunity on one side and to prevent cancer development on the other. This mini review summarizes research advances on the molecular mechanisms regulating the expression of APOBEC3 family members in selected immune cell populations and cancer cells.
载脂蛋白 B mRNA 编辑酶催化多肽样 3（APOBEC3）家族的胞嘧啶脱氨酶在先天免疫中发挥着至关重要的作用，通过脱氨酶和病毒基因组的突变来限制病毒的复制。当 HIV 感染领域的研究发现家族中的一个成员，即 APOBEC3G，限制 T 淋巴细胞中的 HIV 感染，并且病毒感染性因子蛋白驱动该酶的蛋白酶体降解，从而超越其抗病毒功能时，这些蛋白质的抗病毒功能首次被发现。最近癌症基因组学的进展，以及 APOBEC3 酶的生化特征，现在已经将一些家族成员牵连到致癌过程中的体细胞突变中。虽然有几项研究调查了 APOBEC3 表达和活性的下游后果，无论是在病毒感染还是肿瘤发生的情况下，但对于调节 APOBEC3 表达的上游机制知之甚少。这种知识对于开发创新方法来增强抗病毒先天免疫具有重要意义，一方面可以增强抗病毒先天免疫，另一方面可以预防癌症的发生。这篇迷你综述总结了关于调节选定免疫细胞群体和癌细胞中 APOBEC3 家族成员表达的分子机制的研究进展。
