New mTOR Targets Grb Attention

The cellular phosphorylation targets of an important growth promoting enzyme are identified and may provide clinically relevant insights. A cellular enzyme called mechanistic (or mammalian) target of rapamycin (mTOR) controls cell growth and division, and is an important drug target in cancer ( 1 ). Despite extensive study, a complete understanding of mTOR function has remained elusive. One reason is that rapamycin, the natural compound that led to the identification of mTOR, only partially inhibits the enzyme. In addition, mTOR functions in two distinct protein complexes (mTORC1 and mTORC2). Furthermore, only a few proteins have been identified as mTOR substrates, and these seem insufficient to explain its myriad functions. Two papers in this issue, by Hsu et al. on page 1317 ( 2 ) and Yu et al. on page 1322 ( 3 ), uncover dozens of new substrates and downstream targets of mTOR through proteomic screens. These results have major implications for research and drug development in cancer and metabolic disorders.