ABC Transporters in Human Disease and Multidrug Resistan

三磷酸腺苷结合盒(ABC)基因家族编码一组不同的转运蛋白，这些转运蛋白将各种化合物泵送到细胞和组织的膜上。几种人类ABC转运蛋白在对化疗药物具有耐药性的肿瘤细胞中过度表达。我们已经证明ABCA3基因在新生儿呼吸衰竭儿童中发生了突变。这些患者在肺表面活性物质的产生方面存在缺陷，肺表面活性物质是一种由肺泡II型细胞产生的富含脂质的分泌物。轻度感染的患者被发现存在错义突变，这些突变可能具有部分功能。ABC家族的一个新成员已被鉴定为ABCC13。这个基因在类人猿中是假基因，但在狗和猴子的基因组中是一个功能基因。我们还鉴定了小鼠基因组中的ABCA14、ABCA15和ABCA16基因。这些基因只在睾丸中表达。对重要的药物转运体ABCG2基因的突变分析揭示了与蛋白质二聚化有关的残基。ABCG2是以转运蛋白的形式表达的，必须形成二聚体才能产生功能蛋白。抑制这种转运蛋白或其二聚化的药物可以用来抑制癌细胞的生长，可能对癌症干细胞特别有用。

The ATP-binding cassette (ABC) gene family encodes a diverse group of transporter proteins that pump a wide variety of compounds across the membranes of cells and tissues. Several human ABC transporters are overexpressed in tumor cells that are resistant to chemotherapy drugs. We have demonstrated that the ABCA3 gene is mutated in children with neonatal respiratory failure. These patients have defects in the production of lung surfactant, a lipid rich secretion produced by alveolal type II cells. Mildly affected patients were identified that have missense mutations that may be partially functional. A new member of the ABC family has been characterized, ABCC13. This gene is a pseudogene in apes, but is a functional gene in the dog and monkey genomes. We have also characterized the ABCA14, ABCA15, and ABCA16 genes in the mouse genome. These genes are exclusively expressed in the testes. Analysis of mutations in the ABCG2 gene, an important drug transporter, reveals residues that are involved in the dimerization of the protein. ABCG2 is expressed as a transporter, and dimmers must form to generate a functional protein. Drugs that inhibit this transporter, or its dimerization could be used to inhibit the growth of cancer cells, and might be particularly useful against cancer stem cells.