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可变剪接:扩大主要 ABC 和 SLC 药物转运体的多样性。

Alternative Splicing: Expanding Diversity in Major ABC and SLC Drug Transporters.

机构信息

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.

出版信息

AAPS J. 2017 Nov;19(6):1643-1655. doi: 10.1208/s12248-017-0150-0. Epub 2017 Oct 2.

Abstract

Alternative splicing is an important mechanism of genetic regulation enhancing diversity and complexity of the transcriptome and proteome from the finite number of genes. Many reported cases demonstrate that alternative splicing events can lead to changes in the expression/function of proteins during disease development and progression. For pharmacogenes that can influence drug disposition and response, the role of alternative splicing has begun to receive increasing attention as an under-explored source of variable drug response. Here, we provide an overview of alternative spliced variants reported for the major drug transporters of SLC and ABC families with their possible implications in disease and drug therapy. As more comprehensive analyses on the abundance and functional outcomes of variably spliced isoforms of major drug transporters become available, it will be possible to utilize the obtained knowledge as novel therapeutic targets for tailored treatment strategies.

摘要

可变剪接是遗传调控的一种重要机制,可增强转录组和蛋白质组的多样性和复杂性,而这些转录组和蛋白质组均源自有限数量的基因。有许多报道的案例表明,可变剪接事件可导致疾病发生和发展过程中蛋白质表达/功能的变化。对于可影响药物处置和反应的药物基因,可变剪接作为药物反应可变的一个尚未充分探索的来源,其作用开始受到越来越多的关注。在这里,我们概述了 SLC 和 ABC 家族的主要药物转运体的报告可变剪接变体及其在疾病和药物治疗中的可能影响。随着对主要药物转运体的可变剪接异构体丰度和功能结果的更全面分析的出现,有可能将获得的知识用作针对特定治疗策略的新型治疗靶标。

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