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FAM65B controls the proliferation of transformed and primary T cells

Cell quiescence is controlled by regulated genome-encoded programs that actively express genes which are often down-regulated or inactivated in transformed cells. Among them is FoxO1, a transcription factor that imposes quiescence in several cell types, including T lymphocytes. In these cells, the F...

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Autores principales: Froehlich, Jeanne, Versapuech, Margaux, Megrelis, Laura, Largeteau, Quitterie, Meunier, Sylvain, Tanchot, Corinne, Bismuth, Georges, Delon, Jérôme, Mangeney, Marianne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325358/
https://www.ncbi.nlm.nih.gov/pubmed/27556504
http://dx.doi.org/10.18632/oncotarget.11438
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author Froehlich, Jeanne
Versapuech, Margaux
Megrelis, Laura
Largeteau, Quitterie
Meunier, Sylvain
Tanchot, Corinne
Bismuth, Georges
Delon, Jérôme
Mangeney, Marianne
author_facet Froehlich, Jeanne
Versapuech, Margaux
Megrelis, Laura
Largeteau, Quitterie
Meunier, Sylvain
Tanchot, Corinne
Bismuth, Georges
Delon, Jérôme
Mangeney, Marianne
author_sort Froehlich, Jeanne
collection PubMed
description Cell quiescence is controlled by regulated genome-encoded programs that actively express genes which are often down-regulated or inactivated in transformed cells. Among them is FoxO1, a transcription factor that imposes quiescence in several cell types, including T lymphocytes. In these cells, the FAM65B encoding gene is a major target of FOXO1. Here, we show that forced expression of FAM65B in transformed cells blocks their mitosis because of a defect of the mitotic spindle, leading to G2 cell cycle arrest and apoptosis. Upon cell proliferation arrest, FAM65B is engaged in a complex containing two proteins well known to be involved in cell proliferation i.e. the HDAC6 deacetylase and the 14.3.3 scaffolding protein. In primary T cells, FAM65B is down-regulated upon T cell receptor engagement, and maintaining its expression blocks their proliferation, establishing that the decrease of FAM65B expression is required for proliferation. Conversely, inhibiting FAM65B expression in naive T lymphocytes decreases their activation threshold. These results identify FAM65B as a potential new target for controlling proliferation of both transformed and normal cells.
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spelling pubmed-53253582017-03-23 FAM65B controls the proliferation of transformed and primary T cells Froehlich, Jeanne Versapuech, Margaux Megrelis, Laura Largeteau, Quitterie Meunier, Sylvain Tanchot, Corinne Bismuth, Georges Delon, Jérôme Mangeney, Marianne Oncotarget Research Paper Cell quiescence is controlled by regulated genome-encoded programs that actively express genes which are often down-regulated or inactivated in transformed cells. Among them is FoxO1, a transcription factor that imposes quiescence in several cell types, including T lymphocytes. In these cells, the FAM65B encoding gene is a major target of FOXO1. Here, we show that forced expression of FAM65B in transformed cells blocks their mitosis because of a defect of the mitotic spindle, leading to G2 cell cycle arrest and apoptosis. Upon cell proliferation arrest, FAM65B is engaged in a complex containing two proteins well known to be involved in cell proliferation i.e. the HDAC6 deacetylase and the 14.3.3 scaffolding protein. In primary T cells, FAM65B is down-regulated upon T cell receptor engagement, and maintaining its expression blocks their proliferation, establishing that the decrease of FAM65B expression is required for proliferation. Conversely, inhibiting FAM65B expression in naive T lymphocytes decreases their activation threshold. These results identify FAM65B as a potential new target for controlling proliferation of both transformed and normal cells. Impact Journals LLC 2016-08-20 /pmc/articles/PMC5325358/ /pubmed/27556504 http://dx.doi.org/10.18632/oncotarget.11438 Text en Copyright: © 2016 Froehlich et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Froehlich, Jeanne
Versapuech, Margaux
Megrelis, Laura
Largeteau, Quitterie
Meunier, Sylvain
Tanchot, Corinne
Bismuth, Georges
Delon, Jérôme
Mangeney, Marianne
FAM65B controls the proliferation of transformed and primary T cells
title FAM65B controls the proliferation of transformed and primary T cells
title_full FAM65B controls the proliferation of transformed and primary T cells
title_fullStr FAM65B controls the proliferation of transformed and primary T cells
title_full_unstemmed FAM65B controls the proliferation of transformed and primary T cells
title_short FAM65B controls the proliferation of transformed and primary T cells
title_sort fam65b controls the proliferation of transformed and primary t cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325358/
https://www.ncbi.nlm.nih.gov/pubmed/27556504
http://dx.doi.org/10.18632/oncotarget.11438
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