AI Article Synopsis
- The target of rapamycin (TOR) functions in two complexes, TORC1 and TORC2, with only TORC1 being inhibited by rapamycin and more understood in terms of its functions and drug targeting.
- Research efforts are intensifying around TORC2, with new small molecules enabling its acute inhibition and recent structural studies shedding light on its workings.
- Findings from tissue-specific mTORC2 knockout mice are enhancing our understanding of the structure-function relationships in TORC2, suggesting it could become a valuable clinical target in the future.
Article Abstract
The target of rapamycin (TOR) kinase functions in two multiprotein complexes, TORC1 and TORC2. Although both complexes are evolutionarily conserved, only TORC1 is acutely inhibited by rapamycin. Consequently, only TORC1 signaling is relatively well understood; and, at present, only mammalian TORC1 is a validated drug target, pursued in immunosuppression and oncology. However, the knowledge void surrounding TORC2 is dissipating. Acute inhibition of TORC2 with small molecules is now possible and structural studies of both TORC1 and TORC2 have recently been reported. Here we review these recent advances as well as observations made from tissue-specific mTORC2 knockout mice. Together these studies help define TORC2 structure-function relationships and suggest that mammalian TORC2 may one day also become a bona fide clinical target.
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| http://dx.doi.org/10.1016/j.tibs.2016.04.001 | DOI Listing |
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