Modulation of the ATPase and transport activities of broad-acting multidrug resistance factor ABCC10 (MRP7).

ABSTRACT: The cell surface molecule ABCC10 is a broad-acting transporter of xenobiotics, including cancer drugs, such as taxanes, epothilone B, and modulators of the estrogen pathway. Abcc10(-/-) mice exhibit increased tissue sensitivity and lethality resulting from paclitaxel exposure compared with wild-type counterparts, arguing ABCC10 functions as a major determinant of taxane sensitivity in mice. To better understand the mechanistic basis of ABCC10 action, we characterized the biochemical and vectorial transport properties of this protein. Using crude membranes in an ABCC10 overexpression system, we found that the ABCC10 transport substrates estrogen estradiol-glucuronide (E(2)17βG) and leukotriene C4 (LTC(4)) significantly stimulated ABCC10 beryllium fluoride (BeFx)-sensitive ATPase activity. W

SUBMITTER: Malofeeva EV 

PROVIDER: S-EPMC3525726 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature