Amino acid deprivation inhibits TORC1 through a GTPase-activating protein complex for the rag family GTPase Gtr1
- Panchaud, Nicolas Department of Biology, Division of Biochemistry, University of Fribourg, Switzerland
- Péli-Gulli, Marie-Pierre Department of Biology, Division of Biochemistry, University of Fribourg, Switzerland
- De Virgilio, Claudio Department of Biology, Division of Biochemistry, University of Fribourg, Switzerland
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28.05.2013
Published in:
- Science Signaling. - 2013, vol. 6, no. 277, p. ra42
English
The Rag family of guanosine triphosphatases (GTPases) regulates eukaryotic cell growth in response to amino acids by activating the target of rapamycin complex 1 (TORC1). In humans, this pathway is often deregulated in cancer. In yeast, amino acids promote binding of GTP (guanosine 5'-triphosphate) to the Rag family GTPase Gtr1, which, in combination with a GDP (guanosine diphosphate)–bound Gtr2, forms the active, TORC1-stimulating GTPase heterodimer. We identified Iml1, which functioned in a complex with Npr2 and Npr3, as a GAP (GTPase-activating protein) for Gtr1. Upon amino acid deprivation, Iml1 transiently interacted with Gtr1 at the vacuolar membrane to stimulate its intrinsic GTPase activity and consequently decrease the activity of TORC1. Our results delineate a potentially conserved mechanism by which the Iml1, Npr2, and Npr3 orthologous proteins in humans may suppress tumor formation.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Biologie
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 32303
- DOI 10.1126/scisignal.2004112
- Persistent URL
- https://folia.unifr.ch/unifr/documents/303073
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