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FOXP1 acts through a negative feedback loop to suppress FOXO-induced apoptosis

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Año de publicación 2013
Idioma Inglés
Publicado por Cell Death and Differentiation; Vol. 20

Descripción: Transcriptional activity of Forkhead box transcription factor class O (FOXO) proteins can result in a variety of cellular outcomes depending on cell type and activating stimulus. These transcription factors are negatively regulated by the phosphoinositol 3-kinase (PI3K)–protein kinase B (PKB) signaling pathway, which is thought to have a pivotal role in regulating survival of tumor cells in a variety of cancers. Recently, it has become clear that FOXO proteins can promote resistance to anti-cancer therapeutics, designed to inhibit PI3K–PKB activity, by inducing the expression of proteins that provide feedback at different levels of this pathway. We questioned whether such a feedback mechanism may also exist directly at the level of FOXO-induced transcription. To identify critical modulators of FOXO transcriptional output, we performed gene expression analyses after conditional activation of key components of the PI3K–PKB–FOXO signaling pathway and identified FOXP1 as a direct FOXO transcriptional target. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that FOXP1 binds enhancers that are pre-occupied by FOXO3. By sequencing the transcriptomes of cells in which FOXO is specifically activated in the absence of FOXP1, we demonstrate that FOXP1 can modulate the expression of a specific subset of FOXO target genes, including inhibiting expression of the pro-apoptotic gene BIK. FOXO activation in FOXP1-knockdown cells resulted in increased cell death, demonstrating that FOXP1 prevents FOXO-induced apoptosis. We therefore propose that FOXP1 represents an important modulator of FOXO-induced transcription, promoting cellular survival.
Citación recomendada (normas APA)
: María Catalina; Boxtel Gómez Puerto, "FOXP1 acts through a negative feedback loop to suppress FOXO-induced apoptosis", -:Cell Death and Differentiation; Vol. 20, 2013. Consultado en línea en la Biblioteca Digital de Bogotá (https://www.bibliotecadigitaldebogota.gov.co/resources/2087631/), el día 2025-07-01.

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- Otros
- Medicina
Derechos de uso Derechos reservados
Fuente Biblioteca Virtual Banco de la República
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Año de publicación 2013
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FOXP1 acts through a negative feedback loop to suppress FOXO-induced apoptosis

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