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Updated: Jan 26, 2026
In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
Published on: January 22, 2020
A novel regulatory circuit between p53 and GFI1 controls induction of apoptosis in T cells
Charles Vadnais1, Riyan Chen1, Jennifer Fraszczak1
1Institut de recherches cliniques de Montréal (IRCM), Montréal, QC, Canada.
Abstract:
Here we demonstrate a mode of reciprocal regulation between GFI1 and p53 that controls the induction of apoptosis in T cells. We show that GFI1 prevents induction of p53 dependent apoptosis by recruiting LSD1 to p53, which leads to the demethylation of its C-terminal domain. This is accompanied by a decrease of the acetylation of lysine 117 within the core domain of the murine p53 protein, which is required for transcriptional induction of apoptosis. Our results support a model in which the effect of GFI1's regulation of methylation at the c-terminus of p53 is ultimately mediated through control of acetylation at lysine 117 of p53. We propose that GFI1 acts prior to the occurrence of DNA damage to affect the post-translational modification state and limit the subsequent activation of p53. Once activated, p53 then transcriptionally activates GFI1, presumably in order to re-establish the homeostatic balance of p53 activity. These findings have implications for the activity level of p53 in various disease contexts where levels of GFI1 are either increased or decreased.
Insights
Growth factor independence 1 (GFI1) regulates apoptosis in T cells by controlling the tumor suppressor p53. GFI1 limits p53 activation through post-translational modifications, maintaining cellular homeostasis.
Area of Science:
- Cellular Biology
- Molecular Biology
- Immunology
Background:
- The tumor suppressor p53 plays a critical role in apoptosis and cellular stress responses.
- Growth factor independence 1 (GFI1) is a transcription factor involved in various cellular processes.
- The interplay between GFI1 and p53 in regulating T cell apoptosis is not fully understood.
Purpose of the Study:
- To elucidate the mechanism of reciprocal regulation between GFI1 and p53 in T cells.
- To investigate how GFI1 influences p53-dependent apoptosis.
- To understand the role of post-translational modifications in this regulatory pathway.
Main Methods:
- Investigated the interaction between GFI1 and p53.
- Assessed the role of Lysine Specific Demethylase 1 (LSD1) in p53 modification.
- Analyzed changes in p53 acetylation and demethylation.
- Studied the impact of GFI1 on p53 transcriptional activity.
Main Results:
- GFI1 prevents p53-dependent apoptosis by recruiting LSD1 to p53.
- This recruitment leads to demethylation of p53's C-terminal domain and decreased acetylation at lysine 117.
- Acetylation at lysine 117 is crucial for the transcriptional induction of apoptosis.
- p53 activation leads to transcriptional activation of GFI1, suggesting a feedback loop.
Conclusions:
- GFI1 regulates p53 activity by modulating its post-translational modifications, specifically demethylation and acetylation.
- This regulation occurs prior to DNA damage, limiting p53 activation and maintaining T cell homeostasis.
- The findings reveal a novel regulatory axis with implications for p53 activity in disease states associated with altered GFI1 levels.
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