洪梅, 王旭阳. 药物转运体的翻译后处置及相关关键位点研究进展[J]. 华南农业大学学报, 2022, 43(6): 160-172. DOI: 10.7671/j.issn.1001-411X.202206051
    引用本文: 洪梅, 王旭阳. 药物转运体的翻译后处置及相关关键位点研究进展[J]. 华南农业大学学报, 2022, 43(6): 160-172. DOI: 10.7671/j.issn.1001-411X.202206051
    HONG Mei, WANG Xuyang. Current advances on post-translational processing and related essential domains of drug transporters[J]. Journal of South China Agricultural University, 2022, 43(6): 160-172. DOI: 10.7671/j.issn.1001-411X.202206051
    Citation: HONG Mei, WANG Xuyang. Current advances on post-translational processing and related essential domains of drug transporters[J]. Journal of South China Agricultural University, 2022, 43(6): 160-172. DOI: 10.7671/j.issn.1001-411X.202206051

    药物转运体的翻译后处置及相关关键位点研究进展

    Current advances on post-translational processing and related essential domains of drug transporters

    • 摘要: 药物转运体介导种类不同、结构各异的药物跨越细胞膜,影响药物在各组织器官中的浓度以及系统暴露量,不但是影响药效的关键因素,也是重要的药物−药物相互作用位点。人体中关键的药物转运体属于ABC结合盒 (ATP-binding cassette) 超家族或溶质载体 (Solute carrier) 超家族,分别介导细胞对药物的外排和吸收,两者协同作用,共同决定细胞内的药物浓度。作为膜蛋白,药物转运体在翻译后需要经过一系列复杂而精细的调控才能到达作用位点,发挥功能。此外,人体在药物的摄取过程中需要作出快速应对,因此往往以翻译后修饰的方式进行响应;而病理条件下转运体的功能也可能因细胞中各翻译后调控机制的非常态化而受到影响。明确药物转运体的翻译后处置过程,对于解析转运体药物转运的分子机制、阐明遗传多态性造成的个体药物响应差异有重要意义。本文对目前药物转运体的翻译后加工和修饰的相关研究进行了综述,也对在这些调控过程中发挥关键作用的转运体基序和位点进行了总结。

       

      Abstract: Drug transporters mediate different types of drugs with diverse structures across cell membranes, affecting concentration of drugs in various tissues and organs and the systemic exposure. They are not only key factors that determine drug efficacy, but also important sites for drug-drug interaction. The major human drug transporters belong to the ATP-binding cassette (ABC) superfamily or the solute carrier superfamily, which mediate the efflux and absorption of drugs, respectively. These two kinds of transporters coordinate with each other and work in concert to determine intracellular drug concentrations. As membrane proteins, drug transporters need to go through a series of precise and complicated post-translational modifications before arriving at the site of action. Additionally, the human body needs to respond promptly during the intake of drugs and post-translational regulations hence become the manner of choice in such a process; The function of transporters may be affected by the abnormality of various post-translational regulatory mechanisms under pathological conditions as well. Therefore, a comprehensive understanding of the post-translational processing of drug transporters is of great importance for investigating the molecular mechanism(s) of drug transport and clarifying the inter-individual variability of drug response caused by genetic polymorphisms. The present article reviewed current reports on post-translational processing and modification of drug transporters, and summarized essential motifs and/or sites in transporters that play key roles in these regulatory processes.

       

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