Mo Wei, Zhang Jian-Ting
Department of Pharmacology and Toxicology and IU Simon Cancer Center, Indiana University School of Medicine Indianapolis, IN 46202, USA.
Int J Biochem Mol Biol. 2012;3(1):1-27. Epub 2011 Mar 30.
Human ABCG2 is a member of the ATP-binding cassette (ABC) transporter superfamily and is known to contribute to multidrug resistance (MDR) in cancer chemotherapy. Among ABC transporters that are known to cause MDR, ABCG2 is particularly interesting for its potential role in protecting cancer stem cells and its complex oligomeric structure. Recent studies have also revealed that the biogenesis of ABCG2 could be modulated by small molecule compounds. These modulators, upon binding to ABCG2, accelerate the endocytosis and trafficking to lysosome for degradation and effectively reduce the half-life of ABCG2. Hence, targeting ABCG2 stability could be a new venue for therapeutic discovery to sensitize drug resistant human cancers. In this report, we review recent progress on understanding the structure, function, biogenesis, as well as physiological and pathophysiological functions of ABCG2.
人类ABCG2是ATP结合盒（ABC）转运蛋白超家族的成员，已知其在癌症化疗中导致多药耐药（MDR）。在已知会导致MDR的ABC转运蛋白中，ABCG2因其在保护癌症干细胞中的潜在作用及其复杂的寡聚结构而特别引人关注。最近的研究还表明，小分子化合物可以调节ABCG2的生物合成。这些调节剂与ABCG2结合后，会加速内吞作用并转运至溶酶体进行降解，从而有效缩短ABCG2的半衰期。因此，靶向ABCG2的稳定性可能是治疗耐药性人类癌症的新治疗靶点。在本报告中，我们综述了关于ABCG2的结构、功能、生物合成以及生理和病理生理功能的最新研究进展。
