FAM65B controls the proliferation of transformed and primary T cells

// Jeanne Froehlich 1, 2, 3 , Margaux Versapuech 1, 2, 3 , Laura Megrelis 1, 2, 3 , Quitterie Largeteau 1, 2, 3 , Sylvain Meunier 4 , Corinne Tanchot 4 , Georges Bismuth 1, 2, 3 , Jerome Delon 1, 2, 3, * , Marianne Mangeney 1, 2, 3, * 1 Inserm, Institut Cochin, Paris, France 2 Cnrs, Paris, France 3 Universite Paris Descartes, Sorbonne Paris Cite, Paris, France 4 Inserm, PARCC, Universite Paris Descartes, Sorbonne Paris Cite, Paris, France * These authors have contributed equally to this work Correspondence to: Marianne Mangeney, email: marianne.mangeney@inserm.fr Keywords: cell proliferation, cell cycle, signaling, T lymphocytes, leukemia Received: April 13, 2016      Accepted: August 10, 2016      Published: August 20, 2016 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.