A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function.
A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function.
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DOI：
10.1016/j.bbapap.2009.02.014
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Gottesman MM
中科院分区：
文献类型：
--
作者：
Fung KL;Gottesman MM
MDR1（ABCB 1）基因编码一种膜结合转运蛋白，可主动从细胞中排出多种化合物。多药耐药癌细胞MDR1的过度表达是化疗的严重障碍。MDR1在各种组织中表达，以保护它们免受毒素的不利影响。也是MDR1底物的药物的药代动力学也影响疾病结果和治疗效果。虽然MDR1是一个高度保守的基因，但越来越多的证据表明其多态性影响底物特异性。三个单核苷酸多态性（SNP）频繁发生并且具有强连锁，在位置1236C>T（G412G）、2677G>T（A893S）和3435C>T（I1145I）处产生共同的单倍型。同义的3435C>T多态性的频率已被证明根据种族而显著变化。现有文献表明，单倍型在药物反应和疾病易感性中起作用。本文就MDR1基因3435C>T多态性及其单倍型的研究进展作一综述。一个可能的分子作用机制，核糖体失速，可以改变蛋白质的结构和功能，通过改变蛋白质折叠进行了讨论。
The MDR1 (ABCB1) gene encodes a membrane-bound transporter that actively effluxes a wide range of compounds from cells. The overexpression of MDR1 by multidrug-resistant cancer cells is a serious impediment to chemotherapy. MDR1 is expressed in various tissues to protect them from the adverse effect of toxins. The pharmacokinetics of drugs that are also MDR1 substrates also influence disease outcome and treatment efficacy. Although MDR1 is a well conserved gene, there is increasing evidence that its polymorphisms affect substrate specificity. Three single nucleotide polymorphisms (SNPs) occur frequently and have strong linkage, creating a common haplotype at positions 1236C>T (G412G), 2677G>T (A893S) and 3435C>T (I1145I). The frequency of the synonymous 3435C>T polymorphism has been shown to vary significantly according to ethnicity. Existing literature suggests that the haplotype plays a role in response to drugs and disease susceptibility. This review summarizes recent findings on the 3435C>T polymorphism of MDR1 and the haplotype to which it belongs. A possible molecular mechanism of action by ribosome stalling that can change protein structure and function by altering protein folding is discussed.
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DOI：
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发表时间：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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