FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons
By J. Gilley, P. Coffer, J. Ham. Journal of Cell Biology, 2003
709 citations recorded by the source corpus.
Developing sympathetic neurons die by apoptosis when deprived of NGF. BIM, a BH3-only member of the BCL-2 family, is induced after NGF withdrawal in these cells and contributes to NGF withdrawal–induced death. Here, we have investigated the involvement of the Forkhead box, class O (FOXO) subfamily of Forkhead transcription factors in the regulation of BIM expression by NGF. We find that overexpression of FOXO transcription factors induces BIM expression and promotes death of sympathetic neurons in a BIM-dependent manner. In addition, we find that FKHRL1 (FOXO3a) directly activates the bim promoter via two conserved FOXO binding sites and that mutation of these sites abolishes bim promoter activation after NGF withdrawal. Finally, we show that FOXO activity contributes to the NGF deprivation–induced death of sympathetic neurons.
Subfields: Molecular Biology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/c455814dbabc6f61742b747f6fdb5fff745f7e85
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In Molecular Biology
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In Pathology and Forensic Medicine
Citations in the corpus
- Cell Death Signaling. (2015, background): “…JNK Apoptosis Lei and Davis 2003; Putcha et al. 2003 Growth factor or cytokine deprivation Transcription FOXO3a Apoptosis Dijkers et al. 2000; Gilley et al. 2003 Noxa DNA damage Transcription p53 Apoptosis Oda et al. 2000; Villunger et al. 2003; Naik et al. 2007 DNA damage Transcription…”
- A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. (2006, positive): “The FOXO3 target gene bim encodes a BH3-only protein that directly activates the cell death machinery (Gilley et al., 2003).”
- FoxO transcription factors in the maintenance of cellular homeostasis during aging. (2008, background): “FoxO-dependent transcription plays an important role in a wide variety of cellular outputs, including glucose metabolism, cell cycle arrest, differentiation, detoxification of reactive oxygen species (ROS), repair of damaged DNA, and apoptosis [17–26].”
- Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5 (2008, background): “Consistently with the observed regulation of FoxO1 activity, the expression of several FoxO1-upregulated target genes ( Bcl-2-interacting mediator of cell death ( bim”
- The JNK signal transduction pathway. (2007, background): “JNK-stimulated activation of FOXO transcription factors [63 ,64] may also contribute to the increased Bim expression [65].”
- FOXO transcription factors at the interface between longevity and tumor suppression (2005, background): “Cell death The expression of constitutively nuclear forms of FOXO proteins trigger cell death, particularly in neurons and in lymphocytes (Brunet et al., 1999; Zheng et al., 2000; Dijkers et al., 2002; Gilley et al., 2003).”