The interesting relationship between APOBEC3 deoxycytidine deaminases and cancer: a long road ahead.
The interesting relationship between APOBEC3 deoxycytidine deaminases and cancer: a long road ahead.
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DOI：
10.1098/rsob.200188
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发表时间：
2020-12
期刊：
影响因子：
5.8
通讯作者：
Chelico L
中科院分区：
文献类型：
--
作者：
Granadillo Rodríguez M;Flath B;Chelico L
癌症被认为是一组以异常细胞的不受控制的生长和扩散为特征的疾病，并且由体细胞突变推动。载脂蛋白B mRNA编辑酶催化多肽样3（APOBEC 3）酶家族是在多种人类癌症中发现的体细胞突变的内源性来源。虽然这些酶通常作为针对病毒的内在免疫防御，但它们也可以催化基因组单链DNA中间体中的“脱靶”胞苷脱氨基。胞嘧啶的脱氨作用形成尿嘧啶，尿嘧啶在DNA中具有致突变作用。触发APOBEC“脱靶”活性的关键因素是在非正常细胞类型中的过表达、核定位和复制应激。由此产生的尿嘧啶诱导的突变有助于基因组变异，这可能导致癌症的中性，有益或有害的后果。本文综述了APOBEC3酶活性的功能和生化基础，并强调了它们与在此特定背景下研究最充分的癌症（如乳腺癌、肺癌、膀胱癌和人乳头瘤病毒相关癌症）的关系。我们专注于APOBEC3A，APOBEC3B和APOBEC3H单倍型I，因为它们是这些和其他癌症中体细胞突变来源的主要候选者。此外，我们还讨论了APOBEC3表达在耐药性和治疗反应中的预后价值。
Cancer is considered a group of diseases characterized by uncontrolled growth and spread of abnormal cells and is propelled by somatic mutations. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of enzymes are endogenous sources of somatic mutations found in multiple human cancers. While these enzymes normally act as an intrinsic immune defence against viruses, they can also catalyse ‘off-target’ cytidine deamination in genomic single-stranded DNA intermediates. The deamination of cytosine forms uracil, which is promutagenic in DNA. Key factors to trigger the APOBEC ‘off-target’ activity are overexpression in a non-normal cell type, nuclear localization and replication stress. The resulting uracil-induced mutations contribute to genomic variation, which may result in neutral, beneficial or harmful consequences for the cancer. This review summarizes the functional and biochemical basis of the APOBEC3 enzyme activity and highlights their relationship with the most well-studied cancers in this particular context such as breast, lung, bladder, and human papillomavirus-associated cancers. We focus on APOBEC3A, APOBEC3B and APOBEC3H haplotype I because they are the leading candidates as sources of somatic mutations in these and other cancers. Also, we discuss the prognostic value of the APOBEC3 expression in drug resistance and response to therapies.
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影响因子：
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