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

Isabel A. Calvo; Shalini Sharma; Joao A. Paulo; Alexander O.D. Gulka; Andras Boeszoermenyi; Jingyu Zhang; Jose M. Lombana; Christina M. Palmieri; Laura A. Laviolette; Haribabu Arthanari; Othon Iliopoulos; Steven P. Gygi; Mo Motamedi

iScience (Nov 2021)

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

Isabel A. Calvo,
Shalini Sharma,
Joao A. Paulo,
Alexander O.D. Gulka,
Andras Boeszoermenyi,
Jingyu Zhang,
Jose M. Lombana,
Christina M. Palmieri,
Laura A. Laviolette,
Haribabu Arthanari,
Othon Iliopoulos,
Steven P. Gygi,
Mo Motamedi

Affiliations

Isabel A. Calvo: Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA
Shalini Sharma: Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA
Joao A. Paulo: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Alexander O.D. Gulka: Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA
Andras Boeszoermenyi: Department of Biochemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA
Jingyu Zhang: Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA
Jose M. Lombana: Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA
Christina M. Palmieri: Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA
Laura A. Laviolette: Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA
Haribabu Arthanari: Department of Biochemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA
Othon Iliopoulos: 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
Steven P. Gygi: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Mo Motamedi: Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA; Corresponding author

Journal volume & issue: Vol. 24, no. 11
p. 103338

Abstract

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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 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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