Related Experiment Video
Updated: Jan 12, 2026
Author Spotlight: Elucidating the Pathways of TFH Cell Differentiation in Acute LCMV Challenges
Published on: April 26, 2024
FAM65B controls the proliferation of transformed and primary T cells
Jeanne Froehlich1,2,3, Margaux Versapuech1,2,3, Laura Megrelis1,2,3
1Inserm, Institut Cochin, 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.
Insights
The gene FAM65B, regulated by FoxO1, halts cancer cell division and induces apoptosis. Its downregulation is crucial for normal T cell proliferation, suggesting FAM65B as a target for controlling cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Cell quiescence involves active gene programs, with FoxO1 transcription factor inducing quiescence in T lymphocytes.
- FAM65B is a key gene targeted by FOXO1 in T cells.
Purpose of the Study:
- To investigate the role of FAM65B in cell proliferation and cell cycle control.
- To identify FAM65B as a potential therapeutic target for managing cell proliferation in both normal and transformed cells.
Main Methods:
- Forced expression of FAM65B in transformed cells.
- Analysis of cell cycle progression, mitotic spindle function, and apoptosis.
- Investigating FAM65B protein complex formation with HDAC6 and 14.3.3 proteins.
- Examining FAM65B expression levels in primary T cells upon T cell receptor engagement.
Main Results:
- Forced FAM65B expression in transformed cells caused mitotic spindle defects, G2 cell cycle arrest, and apoptosis.
- FAM65B forms a complex with HDAC6 and 14.3.3 proteins upon proliferation arrest.
- FAM65B is downregulated upon T cell receptor engagement in primary T cells.
- Sustained FAM65B expression blocked T cell proliferation, while its inhibition lowered the activation threshold of naive T lymphocytes.
Conclusions:
- FAM65B plays a critical role in regulating cell proliferation by affecting mitotic spindle function and cell cycle progression.
- The downregulation of FAM65B is essential for T cell activation and proliferation.
- FAM65B represents a novel therapeutic target for controlling the proliferation of cancer cells and modulating normal immune cell responses.
Related Concept Videos
02:23Abnormal Proliferation
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:16TGF - β Signaling Pathway
01:23Cells of the Adaptive Immune Response
01:24B Cell Activation and Differentiation
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
01:29Somatic to iPS Cell Reprogramming