Editors' ChoiceCell Biology

Limiting mTORC1

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Sci. Signal.  04 Jun 2013:
Vol. 6, Issue 278, pp. ec131
DOI: 10.1126/scisignal.2004390

The mTORC1 protein kinase complex has important functions linking metabolism to cell growth, and its functions are disrupted in common diseases, including cancer and diabetes. Bar-Peled et al. (see the Perspective by Shaw) discovered regulatory components that help turn down signaling by mTORC1 when cells are deprived of amino acids. Two complexes of proteins, GATOR1 and GATOR2, have opposite effects on activity and cellular localization of mTORC1. Components of the GATOR1 complex negatively regulate mTORC1 and appear to function as tumor suppressors. Cancers with loss of GATOR1 function may be particularly amenable to therapeutic strategies that limit activity of mTORC1.

L. Bar-Peled, L. Chantranupong, A. D. Cherniack, W. W. Chen, K. A. Ottina, B. C. Grabiner, E. D. Spear, S. L. Carter, M. Meyerson, D. M. Sabatini, A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 340, 1100–1106 (2013). [Abstract] [Full Text]

R. J. Shaw, GATORs take a bite out of mTOR. Science 340, 1056–1057 (2013). [Abstract] [Full Text]