ABCC1 p.Cys49Gly
Predicted by SNAP2: | A: N (93%), D: D (71%), E: D (53%), F: N (82%), G: N (53%), H: D (53%), I: N (82%), K: D (59%), L: N (82%), M: N (66%), N: N (66%), P: D (63%), Q: D (53%), R: D (59%), S: N (82%), T: N (87%), V: N (93%), W: D (80%), Y: N (53%), |
Predicted by PROVEAN: | A: N, D: D, E: D, F: N, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Breast cancer resistance protein BCRP/ABCG2 regula... Biochem Pharmacol. 2011 Mar 15;81(6):783-92. Epub 2011 Jan 8. Li X, Pan YZ, Seigel GM, Hu ZH, Huang M, Yu AM
Breast cancer resistance protein BCRP/ABCG2 regulatory microRNAs (hsa-miR-328, -519c and -520h) and their differential expression in stem-like ABCG2+ cancer cells.
Biochem Pharmacol. 2011 Mar 15;81(6):783-92. Epub 2011 Jan 8., [PMID:21219875]
Abstract [show]
Recent studies have shown that a number of microRNAs (miRNA or miR) may regulate human breast cancer resistance protein (BCRP/ABCG2), an important efflux transporter responsible for cellular drug disposition, whereas their effects on ABCG2 protein expression are not compared. In this study, we first identified a new proximal miRNA response element (MRE) for hsa-miR-519c within ABCG2 3'-untranslated region (3'UTR) through computational analyses. This miR-519c MRE site was confirmed using dual luciferase reporter assay and site-directed mutagenesis. Immunoblot analyses indicated that ABCG2 protein expression was significantly down-regulated in MCF-7/MX100 cells after transfection with hsa-miR-328- or -519c expression plasmids, and was markedly up-regulated in MCF-7 cells after transfection with miR-328 or -519c antagomir. However, ABCG2 protein expression was unchanged in MCF-7/MX100 cells after transfection with hsa-miR-520h expression plasmids, which was associated with undetectable miR-520h expression. Furthermore, ABCG2 mRNA degradation was accelerated dramatically in cells transfected with miR-519c expression plasmid, suggesting the involvement of mRNA degradation mechanism. Intervention of miR-328 or -519c signaling led to significant change in intracellular mitoxantrone accumulation, as determined by flow cytometry analyses. In addition, we separated RB143 human retinoblastoma cells into stem-like (ABCG2+) and non-stem-like (ABCG2-) populations through immunomagnetic selection, and found that miR-328, -519c and -520h levels were 9-, 15- and 3-fold lower in the ABCG2+ cells, respectively. Our data suggest that miR-519c and -328 have greater impact on ABCG2 expression than miR-520h in MCF-7 human breast cancer cells, and the presence of proximal miR-519c MRE explains the action of miR-519c on shortened ABCG2 3'UTR.
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No. Sentence Comment
55 The QuikChange II site-directed mutagenesis kit (Stratagene, La Jolla, CA) was employed to create an ABCG2 30 UTR mutant that consisted of three nucleotide transitions (A43C, C45A, C49G) at the proximal miR-519c/520h MRE site (Fig. 1A).
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ABCC1 p.Cys49Gly 21219875:55:181
status: NEW