title: 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.
authors.affiliation: Inserm, Institut Cochin, Paris, France.|Cnrs, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Froehlich
authors.affiliation: Inserm, Institut Cochin, Paris, France.|Cnrs, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Margaux
authors.initials: M
authors.lastname: Versapuech
authors.affiliation: Inserm, Institut Cochin, Paris, France.|Cnrs, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Megrelis
authors.affiliation: Inserm, Institut Cochin, Paris, France.|Cnrs, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Quitterie
authors.initials: Q
authors.lastname: Largeteau
authors.affiliation: Inserm, PARCC, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Meunier
authors.affiliation: Inserm, PARCC, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Tanchot
authors.affiliation: Inserm, Institut Cochin, Paris, France.|Cnrs, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Bismuth
authors.affiliation: Inserm, Institut Cochin, Paris, France.|Cnrs, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Delon
authors.affiliation: Inserm, Institut Cochin, Paris, France.|Cnrs, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Mangeney
mesh_terms: D015815:Cell Adhesion Molecules; D002453:Cell Cycle; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D000071161:Forkhead Box Protein O1 / Q000378:metabolism*; D016195:G2 Phase; D005786:Gene Expression Regulation; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D008938:Mitosis; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D011506:Proteins; C104952:RIPOR2 protein, human; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors
keywords: T lymphocytes; cell cycle; cell proliferation; leukemia; signaling