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

Autor:	Calvo IA; Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA., Sharma S; Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA., Paulo JA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Gulka AOD; Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA., Boeszoermenyi A; Department of Biochemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.; Dana-Farber Cancer Institute, Boston, MA 02215, USA., Zhang J; Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA., Lombana JM; Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA., Palmieri CM; Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA., Laviolette LA; Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA., Arthanari H; Department of Biochemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.; Dana-Farber Cancer Institute, Boston, MA 02215, USA., Iliopoulos O; Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA.; Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA., Gygi SP; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Motamedi M; Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2021 Oct 23; Vol. 24 (11), pp. 103338. Date of Electronic Publication: 2021 Oct 23 (Print Publication: 2021).
DOI:	10.1016/j.isci.2021.103338
Abstrakt:	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. Competing Interests: The authors declare no competing interests. (© 2021 The Author(s).)
Databáze:	MEDLINE
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