Velamakanni Saroj, Janvilisri Tavan, Shahi Sanjay, van Veen Hendrik W
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
Mol Pharmacol. 2008 Jan;73(1):12-7. doi: 10.1124/mol.108.038299.
The human breast cancer resistance protein is an ATP-binding cassette (ABC) multidrug transporter that affects the bioavailability of chemotherapeutic drugs and can confer drug resistance on cancer cells. It is the second member of the ABCG subfamily, other members of which are associated with human steroid disorders such as hypercholesterolemia, sitosterolemia, and atherosclerosis. The molecular bases of protein-steroid interactions in ABC transporters are unknown. Here, we identify a steroid-binding element in the membrane domain of ABCG2 with a similarity to steroid hormone/nuclear receptors. The element facilitates steroid hormone binding and mediates modulation of ABCG2 activity. The identification of this element might provide an opportunity for the development of new therapeutic ligands for ABCG2.
人类乳腺癌耐药蛋白是一种ATP结合盒（ABC）多药转运蛋白，它会影响化疗药物的生物利用度，并能赋予癌细胞耐药性。它是ABCG亚家族的第二个成员，该亚家族的其他成员与人类类固醇紊乱有关，如高胆固醇血症、谷甾醇血症和动脉粥样硬化。ABC转运蛋白中蛋白质-类固醇相互作用的分子基础尚不清楚。在这里，我们在ABCG2的膜结构域中鉴定出一个与类固醇激素/核受体相似的类固醇结合元件。该元件促进类固醇激素结合并介导ABCG2活性的调节。这一元件的鉴定可能为开发ABCG2的新型治疗配体提供机会。
