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

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cellular physiology Cell biology Functional aspects of cell biology Science Q
Acceso en línea:	https://doaj.org/article/4fe5db4627e54e2a8a995599fe937e78
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spelling	oai:doaj.org-article:4fe5db4627e54e2a8a995599fe937e782021-11-20T05:10:08ZThe fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability2589-004210.1016/j.isci.2021.103338https://doaj.org/article/4fe5db4627e54e2a8a995599fe937e782021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013079https://doaj.org/toc/2589-0042Summary: 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.Isabel A. CalvoShalini SharmaJoao A. PauloAlexander O.D. GulkaAndras BoeszoermenyiJingyu ZhangJose M. LombanaChristina M. PalmieriLaura A. LavioletteHaribabu ArthanariOthon IliopoulosSteven P. GygiMo MotamediElsevierarticleCellular physiologyCell biologyFunctional aspects of cell biologyScienceQENiScience, Vol 24, Iss 11, Pp 103338- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cellular physiology Cell biology Functional aspects of cell biology Science Q
spellingShingle	Cellular physiology Cell biology Functional aspects of cell biology Science Q 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 The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability
description	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.
format	article
author	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
author_facet	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
author_sort	Isabel A. Calvo
title	The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability
title_short	The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability
title_full	The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability
title_fullStr	The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability
title_full_unstemmed	The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability
title_sort	fission yeast flcn/fnip complex augments torc1 repression or activation in response to amino acid (aa) availability
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/4fe5db4627e54e2a8a995599fe937e78
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The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability

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