کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1392623 | 983760 | 2009 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: A Chemical Genetic Screen for mTOR Pathway Inhibitors Based on 4E-BP-Dependent Nuclear Accumulation of eIF4E A Chemical Genetic Screen for mTOR Pathway Inhibitors Based on 4E-BP-Dependent Nuclear Accumulation of eIF4E](/preview/png/1392623.png)
SummaryThe signal transduction pathway wherein mTOR regulates cellular growth and proliferation is an active target for drug discovery. The search for new mTOR inhibitors has recently yielded a handful of promising compounds that hold therapeutic potential. This search has been limited by the lack of a high-throughput assay to monitor the phosphorylation of a direct rapamycin-sensitive mTOR substrate in cells. Here we describe a novel cell-based chemical genetic screen useful for efficiently monitoring mTOR signaling to 4E-BPs in response to stimuli. The screen is based on the nuclear accumulation of eIF4E, which occurs in a 4E-BP-dependent manner specifically upon inhibition of mTOR signaling. Using this assay in a small-scale screen, we have identified several compounds not previously known to inhibit mTOR signaling, demonstrating that this method can be adapted to larger screens.
Journal: - Volume 16, Issue 12, 24 December 2009, Pages 1240–1249