Format

Send to

Choose Destination
Oncotarget. 2016 Sep 27;7(39):63215-63225. doi: 10.18632/oncotarget.11438.

FAM65B controls the proliferation of transformed and primary T cells.

Author information

1
Inserm, Institut Cochin, Paris, France.
2
Cnrs, Paris, France.
3
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
4
Inserm, PARCC, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

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.

KEYWORDS:

T lymphocytes; cell cycle; cell proliferation; leukemia; signaling

PMID:
27556504
PMCID:
PMC5325358
DOI:
10.18632/oncotarget.11438
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center