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Updated: May 9, 2026
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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
FOXP1 acts through a negative feedback loop to suppress FOXO-induced apoptosis
R van Boxtel1, C Gomez-Puerto, M Mokry
1Department of Cell Biology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands.
Cell Death and Differentiation
|July 9, 2013
Summary
Forkhead box transcription factor class O (FOXO) proteins regulate cell survival. This study identifies FOXP1 as a key regulator that prevents FOXO-induced apoptosis, promoting tumor cell survival.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- Forkhead box transcription factor class O (FOXO) proteins influence diverse cellular functions and are regulated by the phosphoinositol 3-kinase (PI3K)-protein kinase B (PKB) pathway.
- FOXO proteins can confer resistance to anti-cancer therapies by creating feedback loops within the PI3K-PKB pathway.
- The existence of feedback mechanisms directly at the level of FOXO-induced transcription remained unclear.
Purpose of the Study:
- To identify novel modulators of FOXO transcriptional output.
- To investigate the role of FOXP1 in regulating FOXO-mediated transcription and cellular survival.
Main Methods:
- Conditional activation of the PI3K-PKB-FOXO signaling pathway.
- Gene expression analysis and transcriptome sequencing.
- Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq).
Main Results:
- FOXP1 was identified as a direct transcriptional target of FOXO.
- FOXP1 binds to enhancers occupied by FOXO3.
- FOXP1 modulates a subset of FOXO target genes, including inhibition of the pro-apoptotic gene BIK, and prevents FOXO-induced apoptosis.
Conclusions:
- FOXP1 acts as a critical modulator of FOXO transcriptional activity.
- FOXP1 promotes cellular survival by inhibiting FOXO-induced apoptosis.
- FOXP1's role in FOXO signaling has implications for cancer therapeutics targeting the PI3K-PKB pathway.
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