FAM65B controls the proliferation of transformed and primary T cells

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


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.

MeSH terms

  • Cell Adhesion Molecules
  • Cell Cycle
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cells, Cultured
  • Down-Regulation
  • Forkhead Box Protein O1 / metabolism*
  • G2 Phase
  • Gene Expression Regulation
  • Humans
  • Leukemia / metabolism
  • Mitosis
  • Phosphorylation
  • Proteins / metabolism*
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • Spindle Apparatus / metabolism
  • T-Lymphocytes / cytology*
  • Transcription Factors / metabolism


  • Cell Adhesion Molecules
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Proteins
  • RIPOR2 protein, human
  • Receptors, Antigen, T-Cell
  • Transcription Factors