The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability

The target of Rapamycin complex1 (TORC1) senses and integrates several environmental signals, including amino acid (AA) availability, to regulate cell growth. Folliculin (FLCN) is a tumor suppressor (TS) protein in renal cell carcinoma, which paradoxically activates TORC1 in response to AA supplemen...

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Autores: Calvo-Arnedo, I. (Isabel)|||/items/418daa5a-e5cd-4657-bed3-51d603fa8942, Sharma, S. (Shalini)|||/items/b8c4671b-c8d2-4250-9920-dce1b7810cd3, Paulo, J.A. (Joao A.)|||/items/7fe9c54d-b5a6-4ce5-9fc2-a84ad7152a8e, Gulka, A.O.D (Alexander O.D.)|||/items/4a80b68a-024d-453e-9a31-86f86df6c7c0, Boeszoermenyi, A. (Andras)|||/items/b75c160d-6d21-4b81-8edc-0d1434c243a6, Zhang, J. (Jingyu)|||/items/fae3ea75-6833-4537-b6c8-9c6a85d14870, Lombana, J.M. (Jose M.)|||/items/c9f9f3ea-884d-4589-99ad-2076fddc3cd1, Palmieri, C.M. (Christina M.)|||/items/1d44d746-c9de-4fd8-a161-30191d1b428e, Laviolette, L.A. (Laura A.)|||/items/e7040a8b-e7b7-4a1a-a7c4-71178ab8a3b1, Arthanari, H. (Haribabu)|||/items/ddedd22f-d730-45c2-a6bc-3ae57b89d933, Iliopoulos, O. (Othon)|||/items/9e207e71-2d32-400d-a091-99137fc4f467, Gygi, S.P. (Steven P.)|||/items/38cd133b-4aa2-4f8d-be09-3d95d20965eb, Motamedi, M. (Mo)|||/items/94cbe640-0185-4f24-82d4-6c858d6ccf65
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/114667
Acceso en línea:https://hdl.handle.net/10171/114667
Access Level:acceso abierto
Palabra clave:Cell biology
Cellular physiology
Functional aspects of cell biology
Descripción
Sumario:The target of Rapamycin complex1 (TORC1) senses and integrates several environmental signals, including amino acid (AA) availability, to regulate cell growth. Folliculin (FLCN) is a tumor suppressor (TS) protein in renal cell carcinoma, which paradoxically activates TORC1 in response to AA supplementation. Few tractable systems for modeling FLCN as a TS are available. Here, we characterize the FLCN-containing complex in Schizosaccharomyces pombe (called BFC) and show that BFC augments TORC1 repression and activation in response to AA starvation and supplementation, respectively. BFC co-immunoprecipitates V-ATPase, a TORC1 modulator, and regulates its activity in an AA-dependent manner. BFC genetic and proteomic networks identify the conserved peptide transmembrane transporter Ptr2 and the phosphoribosylformylglycinamidine synthase Ade3 as new AA-dependent regulators of TORC1. Overall, these data ascribe an additional repressive function to Folliculin in TORC1 regulation and reveal S. pombe as an excellent system for modeling the AA-dependent, FLCN-mediated repression of TORC1 in eukaryotes.

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