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 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.

Citation

Jeanne Froehlich, Margaux Versapuech, Laura Megrelis, Quitterie Largeteau, Sylvain Meunier, Corinne Tanchot, Georges Bismuth, Jérôme Delon, Marianne Mangeney. FAM65B controls the proliferation of transformed and primary T cells. Oncotarget. 2016 Sep 27;7(39):63215-63225

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PMID: 27556504

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