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Translational Regulation of TRAIL Sensitivity
Amith Panner, Andrew T. Parsa and Russell O. Pieper
volume 5 | issue 2
16 january 2006Pages: 147 - 150
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TNF-related apoptosis-inducing ligand (TRAIL) is a peptide that induces apoptosis to varying degrees in tumor cells, but not in normal cells. While TRAIL sensitivity in tumors has been linked to c-myc- and MEK/Erk-induced enhancement of caspase activation, our recent study identified a third input controlling TRAIL sensitivity, namely the Akt-mTOR pathway. We showed that instead of enhancing TRAIL sensitivity, Akt expression, acting through mTOR and the mTOR targets S6 kinase and eIF-4E, selectively enhances translation of the anti-apoptotic protein FLIPs and confers TRAIL resistance. In this perspective article we will discuss the linkage of the AktmTOR pathway to other regulators of TRAIL sensitivity, its importance in controlling a broader range of apoptotic events, its utility in predicting TRAIL responsiveness, and its potential manipulation for therapeutic benefit.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.