A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1-Reference-Cited by-全球学者库

A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1

Published:2013-05-31 Issue:6136 Volume:340 Page:1100-1106
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Bar-Peled Liron¹²,Chantranupong Lynne¹²,Cherniack Andrew D.³,Chen Walter W.¹²,Ottina Kathleen A.¹²,Grabiner Brian C.¹²,Spear Eric D.⁴,Carter Scott L.³,Meyerson Matthew³⁵⁶,Sabatini David M.¹²⁷³

Affiliation:

1. Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA.

2. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.

3. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Cambridge, MA 02142, USA.

4. Department of Cell Biology, John Hopkins University School of Medicine, Baltimore, MD 21205, USA.

5. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA.

6. Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.

7. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

Limiting mTORC1 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. (p. 1100 ; 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 supressors. Cancers with loss of GATOR1 function may be particularly amenable to therapeutic strategies that limit activity of mTORC1.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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