SIRT1 negatively regulates the mammalian target of rapamycin.

The IGF/mTOR pathway, which is modulated by nutrients, growth factors, energy status and cellular stress regulates aging in various organisms. SIRT1 is a NAD+ dependent deacetylase that is known to regulate caloric restriction mediated longevity in model organisms, and has also been linked to the in...

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Autores principales:	Hiyaa Singhee Ghosh, Michael McBurney, Paul D Robbins
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/efb060382e44476d98825c57eb72c6b9
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spelling	oai:doaj.org-article:efb060382e44476d98825c57eb72c6b92021-11-25T06:25:51ZSIRT1 negatively regulates the mammalian target of rapamycin.1932-620310.1371/journal.pone.0009199https://doaj.org/article/efb060382e44476d98825c57eb72c6b92010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20169165/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The IGF/mTOR pathway, which is modulated by nutrients, growth factors, energy status and cellular stress regulates aging in various organisms. SIRT1 is a NAD+ dependent deacetylase that is known to regulate caloric restriction mediated longevity in model organisms, and has also been linked to the insulin/IGF signaling pathway. Here we investigated the potential regulation of mTOR signaling by SIRT1 in response to nutrients and cellular stress. We demonstrate that SIRT1 deficiency results in elevated mTOR signaling, which is not abolished by stress conditions. The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner. Furthermore, we demonstrate that SIRT1 interacts with TSC2, a component of the mTOR inhibitory-complex upstream to mTORC1, and regulates mTOR signaling in a TSC2 dependent manner. These results demonstrate that SIRT1 negatively regulates mTOR signaling potentially through the TSC1/2 complex.Hiyaa Singhee GhoshMichael McBurneyPaul D RobbinsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 2, p e9199 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiyaa Singhee Ghosh Michael McBurney Paul D Robbins SIRT1 negatively regulates the mammalian target of rapamycin.
description	The IGF/mTOR pathway, which is modulated by nutrients, growth factors, energy status and cellular stress regulates aging in various organisms. SIRT1 is a NAD+ dependent deacetylase that is known to regulate caloric restriction mediated longevity in model organisms, and has also been linked to the insulin/IGF signaling pathway. Here we investigated the potential regulation of mTOR signaling by SIRT1 in response to nutrients and cellular stress. We demonstrate that SIRT1 deficiency results in elevated mTOR signaling, which is not abolished by stress conditions. The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner. Furthermore, we demonstrate that SIRT1 interacts with TSC2, a component of the mTOR inhibitory-complex upstream to mTORC1, and regulates mTOR signaling in a TSC2 dependent manner. These results demonstrate that SIRT1 negatively regulates mTOR signaling potentially through the TSC1/2 complex.
format	article
author	Hiyaa Singhee Ghosh Michael McBurney Paul D Robbins
author_facet	Hiyaa Singhee Ghosh Michael McBurney Paul D Robbins
author_sort	Hiyaa Singhee Ghosh
title	SIRT1 negatively regulates the mammalian target of rapamycin.
title_short	SIRT1 negatively regulates the mammalian target of rapamycin.
title_full	SIRT1 negatively regulates the mammalian target of rapamycin.
title_fullStr	SIRT1 negatively regulates the mammalian target of rapamycin.
title_full_unstemmed	SIRT1 negatively regulates the mammalian target of rapamycin.
title_sort	sirt1 negatively regulates the mammalian target of rapamycin.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/efb060382e44476d98825c57eb72c6b9
work_keys_str_mv	AT hiyaasingheeghosh sirt1negativelyregulatesthemammaliantargetofrapamycin AT michaelmcburney sirt1negativelyregulatesthemammaliantargetofrapamycin AT pauldrobbins sirt1negativelyregulatesthemammaliantargetofrapamycin
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SIRT1 negatively regulates the mammalian target of rapamycin.

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