Detalle Publicación

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

Autores: Calvo Arnedo, Isabel; Sharma, S.; Paulo, J. A.; Gulka, A. O. D.; Boeszoermenyi, A.; Zhang, J.; Lombana, J. M.; Palmieri, C. M.; Laviolette, L. A.; Arthanari, H.; Iliopoulos, O.; Gygi, S. P.; Motamedi, M. (Autor de correspondencia)
Título de la revista: ISCIENCE
ISSN: 2589-0042
Volumen: 24
Número: 11
Páginas: 103338
Fecha de publicación: 2021
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. Fewtractable systems formodeling FLCN-as a TS are available. Here, we characterize the FLCNcontaining 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.