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MRP1(ABCC1) function is regulated via RhoA
Author(s) -
Paumi Christian M.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1015.4
Subject(s) - rhoa , abcc1 , small gtpase , microbiology and biotechnology , function (biology) , multiple drug resistance , immunoprecipitation , biology , cancer research , chemistry , signal transduction , drug resistance , gene , biochemistry , genetics , atp binding cassette transporter , transporter
Multidrug resistance‐associated protein 1 (MRP1/ABCC1) has been shown to play an important role in the cellular efflux of a broad range of endogenous and exogenous toxins. MRP1 expression is associated with multidrug resistance (MDR) in a variety of cancers. Although much is known about MRP1 function and expression, the post‐translational regulation of MRP1 is poorly characterized. Based on work conducted by Paumi et. al. in 2007 that showed that the function of the yeast MRP1 homologue, Ycf1p, is regulated by the yeast homologue of RhoA, Rho1p, via the GTP‐exchange factor, Tus1p; We have examined the role of RhoA and Tus1p homologue, ARHGEF11 (PDZ‐GEF), in the regulation of MRP1 function. Here we show that MRP1 and RhoA interact by Co‐immunoprecipitation and that inhibition of RhoA activity alters MRP1 cellular function. RhoA overexpression in cancer is strongly associated with a poor chemotherapeutic response in patients. Our preliminary data suggests that one mechanism by which RhoA overexpression results in poor chemotherapeutic response is via increasing MRP1 function. CMP is funded by NIH P20RR020171.