%0 Journal Article %T FAM65B controls the proliferation of transformed and primary T cells %+ Institut Cochin (IC UM3 (UMR 8104 / U1016)) %+ Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970) %A Froehlich, Jeanne %A Versapuech, Margaux %A Megrelis, Laura %A Largeteau, Quitterie %A Meunier, Sylvain %A Tanchot, Corinne %A Bismuth, Georges %A Delon, Jérôme %A Mangeney, Marianne %Z This work was granted by La Ligue Nationale Contre le Cancer, CNRS and Inserm. %< avec comité de lecture %@ 1949-2553 %J Oncotarget %I Impact journals %P [Epub ahead of print] %8 2016-09-20 %D 2016 %R 10.18632/oncotarget.11438 %K cell proliferation %K cell cycle %K signaling %K T lymphocytes %K leukemia %Z Life Sciences [q-bio]/Biochemistry, Molecular BiologyJournal articles %X 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. %G English %2 https://inserm.hal.science/inserm-01361856/document %2 https://inserm.hal.science/inserm-01361856/file/11438-173039-1-PB.pdf %2 https://inserm.hal.science/inserm-01361856/file/Suppl%20Fig%20Legends%20Oncotarget2016-File011.pdf %L inserm-01361856 %U https://inserm.hal.science/inserm-01361856 %~ INSERM %~ UNIV-PARIS5 %~ CNRS %~ APHP %~ USPC %~ CHU-UNIV-PARIS5 %~ UNIV-PARIS %~ UP-SANTE