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

Isabel A Calvo1, Shalini Sharma1, Joao A Paulo2

  • 1Massachusetts General Hospital Center for Cancer Research and Department of Medicine Harvard Medical School, Charlestown, MA 02129, USA.

Iscience
|November 22, 2021
PubMed

Insights

Folliculin (FLCN) protein complex in yeast augments the repression and activation of the target of Rapamycin complex1 (TORC1) based on amino acid availability. This study reveals FLCN

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The target of Rapamycin complex1 (TORC1) regulates cell growth by sensing environmental signals like amino acid (AA) availability.
  • Folliculin (FLCN) is a tumor suppressor protein implicated in renal cell carcinoma, paradoxically activating TORC1 upon AA supplementation.
  • Tractable model systems for studying FLCN's tumor suppressor functions are limited.

Purpose of the Study:

  • To characterize the FLCN-containing complex (BFC) in *Schizosaccharomyces pombe* (yeast).
  • To investigate the role of BFC in regulating TORC1 activity in response to varying amino acid availability.
  • To identify novel regulators of TORC1 interacting with the FLCN complex.

Main Methods:

  • Co-immunoprecipitation to identify interacting proteins.
  • Genetic and proteomic network analysis in *S. pombe*.
  • Characterization of BFC's function in TORC1 regulation under different AA conditions.

Main Results:

  • The BFC complex in *S. pombe* enhances TORC1 repression during AA starvation and activation during AA supplementation.
  • BFC interacts with V-ATPase, a known TORC1 modulator, and regulates its activity in an AA-dependent manner.
  • New AA-dependent TORC1 regulators, Ptr2 and Ade3, were identified through BFC's genetic and proteomic networks.

Conclusions:

  • Folliculin (FLCN) possesses an additional repressive function in TORC1 regulation.
  • *S. pombe* serves as an effective model system for studying FLCN-mediated, AA-dependent repression of TORC1 in eukaryotes.
  • The findings provide new insights into the complex regulation of TORC1 by FLCN and its interacting partners.
Keywords:
Cell biologyCellular physiologyFunctional aspects of cell biology

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