کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10769226 | 1050820 | 2005 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Engineered gene over-expression as a method of drug target identification
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
The proposed target of aminobisphosphonate (aBP) bone resorption inhibitors, both in mammalian osteoclasts and in Dictyostelium, is the enzyme farnesyl diphosphate synthase (FDP synthase). The genetic evidence, obtained with Dictyostelium, derives from variant strains that over-express FDP synthase and that are relatively resistant to aBPs. We show that forced FDP synthase over-expression also leads to aBP resistance; by placing FDP synthase under control of a semi-constitutive promoter, transforming it into Dictyostelium cells and selecting with the aBP alendronate. This combination of drug and dominant selectable marker provides a novel selection system for transformation. We further show that, when a population of Dictyostelium cells expressing an entire growth stage cDNA library is placed under alendronate selection, FDP synthase is the only cDNA insert that confers drug resistance. This confirms FDP synthase as the primary target of aBPs and suggests a general method of drug target identification based upon engineered gene over-expression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 334, Issue 2, 26 August 2005, Pages 555-560
Journal: Biochemical and Biophysical Research Communications - Volume 334, Issue 2, 26 August 2005, Pages 555-560
نویسندگان
Christopher J. Sugden, Janine R. Roper, Jeffrey G. Williams,