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Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy

Polymorphic variants of the FTO (fat mass and obesity) gene associate with body mass index in humans, but the underlying molecular mechanisms have not been firmly determined. FTO is linked to energy homeostasis via amino acid sensing and is thought to activate the mammalian target of rapamycin compl...

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Autores principales: Aas, Aleksander, Isakson, Pauline, Bindesbøll, Christian, Alemu, Endalkachew A., Klungland, Arne, Simonsen, Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347998/
https://www.ncbi.nlm.nih.gov/pubmed/28288181
http://dx.doi.org/10.1371/journal.pone.0168182
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author Aas, Aleksander
Isakson, Pauline
Bindesbøll, Christian
Alemu, Endalkachew A.
Klungland, Arne
Simonsen, Anne
author_facet Aas, Aleksander
Isakson, Pauline
Bindesbøll, Christian
Alemu, Endalkachew A.
Klungland, Arne
Simonsen, Anne
author_sort Aas, Aleksander
collection PubMed
description Polymorphic variants of the FTO (fat mass and obesity) gene associate with body mass index in humans, but the underlying molecular mechanisms have not been firmly determined. FTO is linked to energy homeostasis via amino acid sensing and is thought to activate the mammalian target of rapamycin complex 1, a negative regulator of autophagy. FTO localises both to the nucleus and the cytoplasm, and in this study we identify a functional nuclear localisation signal (NLS) in the N-terminus of FTO, as well as nuclear localization information in its very C-terminus. Inhibition of FTO nuclear transport has no effect on autophagy and in contrast to a previously proposed role of FTO in autophagy, we find no difference in starvation-induced autophagy in control cells compared to a panel of cell types depleted of FTO. Future studies that further characterise the cellular functions of FTO will be important to understand why variants in FTO are associated with body weight.
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spelling pubmed-53479982017-03-30 Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy Aas, Aleksander Isakson, Pauline Bindesbøll, Christian Alemu, Endalkachew A. Klungland, Arne Simonsen, Anne PLoS One Research Article Polymorphic variants of the FTO (fat mass and obesity) gene associate with body mass index in humans, but the underlying molecular mechanisms have not been firmly determined. FTO is linked to energy homeostasis via amino acid sensing and is thought to activate the mammalian target of rapamycin complex 1, a negative regulator of autophagy. FTO localises both to the nucleus and the cytoplasm, and in this study we identify a functional nuclear localisation signal (NLS) in the N-terminus of FTO, as well as nuclear localization information in its very C-terminus. Inhibition of FTO nuclear transport has no effect on autophagy and in contrast to a previously proposed role of FTO in autophagy, we find no difference in starvation-induced autophagy in control cells compared to a panel of cell types depleted of FTO. Future studies that further characterise the cellular functions of FTO will be important to understand why variants in FTO are associated with body weight. Public Library of Science 2017-03-13 /pmc/articles/PMC5347998/ /pubmed/28288181 http://dx.doi.org/10.1371/journal.pone.0168182 Text en © 2017 Aas et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Aas, Aleksander
Isakson, Pauline
Bindesbøll, Christian
Alemu, Endalkachew A.
Klungland, Arne
Simonsen, Anne
Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy
title Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy
title_full Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy
title_fullStr Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy
title_full_unstemmed Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy
title_short Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy
title_sort nucleocytoplasmic shuttling of fto does not affect starvation-induced autophagy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347998/
https://www.ncbi.nlm.nih.gov/pubmed/28288181
http://dx.doi.org/10.1371/journal.pone.0168182
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