FAM65B controls the proliferation of transformed and primary T cells
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Jeanne Froehlich1,2,3, Margaux Versapuech1,2,3, Laura Megrelis1,2,3, Quitterie Largeteau1,2,3, Sylvain Meunier4, Corinne Tanchot4, Georges Bismuth1,2,3, Jérôme Delon1,2,3,*, Marianne Mangeney1,2,3,*
1Inserm, Institut Cochin, Paris, France
2Cnrs, Paris, France
3Université Paris Descartes, Sorbonne Paris Cité, Paris, France
4Inserm, PARCC, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
*These authors have contributed equally to this work
Marianne Mangeney, email: [email protected]
Keywords: cell proliferation, cell cycle, signaling, T lymphocytes, leukemia
Received: April 13, 2016 Accepted: August 10, 2016 Published: August 20, 2016
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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