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

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

Blog Article

Summary: 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 Stoles 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 Rangehood Light Cover 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.