کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10759525 | 1050425 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification and functional characterization of novel MATE1 genetic variations in Koreans
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Multidrug and toxin extrusion 1 (MATE1, SLC47A1), an organic cation transporter, plays an important role in the renal and biliary elimination of various clinical drugs, including the anti-diabetic drug metformin. The goal of this study was to identify and characterize novel genetic variants of MATE1. Five variants in the promoter region and two nonsynonymous variants, p.D64G and p.L125F, were identified in 48 DNA samples from healthy Koreans. MATE1 promoter haplotype 3 containing g.â1975C>A showed a significant increase in reporter activity. Three transcription factors, Nkx-2.5, SREBP-1, and USF-1 were predicted to bind to the promoter in the region of g.â1975C>A. Results from electrophoretic mobility shift assays showed that the g.â1975A allele exhibits greater binding affinity to all of these transcription factors than the g.â1975C allele. In particular, we found that Nkx-2.5 and USF-1 induce MATE1 transcription. Our study suggests that the common promoter haplotype of MATE1 changes MATE1 transcriptional activity regulated by Nkx-2.5, SREBP-1, and USF-1.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 434, Issue 2, 3 May 2013, Pages 334-340
Journal: Biochemical and Biophysical Research Communications - Volume 434, Issue 2, 3 May 2013, Pages 334-340
نویسندگان
Tae Hee Kim, Kyoung Hee Kim, Hyo Jin Park, Siyoon Kim, Ji Ha Choi,