FAM65B controls the proliferation of transformed and primary T cells

Abstract : 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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Oncotarget, Impact journals, 2016, [Epub ahead of print]. 〈10.18632/oncotarget.11438〉
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Jeanne Froehlich, Margaux Versapuech, Laura Megrelis, Quitterie Largeteau, Sylvain Meunier, et al.. FAM65B controls the proliferation of transformed and primary T cells. Oncotarget, Impact journals, 2016, [Epub ahead of print]. 〈10.18632/oncotarget.11438〉. 〈inserm-01361856〉

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