Reference - PMID:34805795 - The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability.
Reference summary
- PubMed ID
- PMID:34805795
- Title
- The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability.
- Authors
- Calvo IA, Sharma S, Paulo JA, Gulka AOD, Boeszoermenyi A, Zhang J, Lombana JM, Palmieri CM, Laviolette LA, Arthanari H, Iliopoulos O, Gygi SP, Motamedi M
- Citation
- iScience 2021 Nov 19;24(11):103338
- Publication year
- 2021
- Abstract
- 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.
