ArticleCell death and differentiation2013
A feed-forward loop involving Trib3, Akt and FoxO mediates death of NGF-deprived neurons.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Pseudokinase STK40 promotes TScience advances · 2024Article
- mTORC1 and mTORC2 Co-Protect against Cadmium-Induced Renal Tubular Epithelial Cell Apoptosis and Acute Kidney Injury by Regulating Protein Kinase B.Journal of agricultural and food chemistry · 2024Article
- TRIB3 silencing promotes the downregulation of Akt pathway and PAX3-FOXO1 in high-risk rhabdomyosarcoma.Experimental hematology & oncology · 2024Article
- Non-coding RNAs and Exosomal Non-coding RNAs in Traumatic Brain Injury: the Small Player with Big Actions.Molecular neurobiology · 2023Review
- Autophagy and apoptosis cascade: which is more prominent in neuronal death?Cellular and molecular life sciences : CMLS · 2021Review
- Review
- Review
- A human-specific VNTR in the TRIB3 promoter causes gene expression variation between individuals.PLoS genetics · 2020Article
- Irradiation-Induced Upregulation of miR-711 Inhibits DNA Repair and Promotes Neurodegeneration Pathways.International journal of molecular sciences · 2020Article
- TRIB3 supports breast cancer stemness by suppressing FOXO1 degradation and enhancing SOX2 transcription.Nature communications · 2019Article
- Apoptotic cell death regulation in neurons.The FEBS journal · 2019Review
- Prospects for pharmacological targeting of pseudokinases.Nature reviews. Drug discovery · 2019Review
- Article
- Role of endoplasmic reticulum stress-associated gene TRIB3 in rats following kainic acid-induced seizures.International journal of clinical and experimental pathology · 2019Article
- Inhibition of TRIB3 Protects Against Neurotoxic Injury Induced by Kainic Acid in Rats.Frontiers in pharmacology · 2019Article
- Susceptibility of brain atrophy toProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Capsaicin-induced TRIB3 upregulation promotes apoptosis in cancer cells.Cancer management and research · 2018Article
- A neuroprotective agent that inactivates prodegenerative TrkA and preserves mitochondria.The Journal of cell biology · 2017Article
- The Drosophila melanogaster tribbles pseudokinase is necessary for proper memory formation.Neurobiology of learning and memory · 2017Article
- Nerve growth factor pretreatment inhibits lidocaine‑induced myelin damage via increasing BDNF expression and inhibiting p38 mitogen activation in the rat spinal cord.Molecular medicine reports · 2017Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The mechanisms governing neuron death following NGF deprivation are incompletely understood. Here, we show that Trib3, a protein induced by NGF withdrawal, has a key role in such death via a loop involving the survival kinase Akt and FoxO transcription factors. Trib3 overexpression is sufficient to induce neuron death, and silencing of endogenous Trib3 strongly protects from death when NGF is withdrawn. Mechanism studies reveal that Trib3 interferes with phosphorylation/activity of Akt and contributes to Akt inactivation after NGF deprivation. FoxO1a, a direct Akt substrate, is dephosphorylated upon NGF withdrawal and consequently undergoes nuclear translocation and activates pro-apoptotic genes. We find that Trib3 is required for FoxO1a dephosphorylation and nuclear translocation after NGF deprivation. Conversely, Trib3 induction requires FoxO transcription factors, which show enhanced occupancy of the Trib3 promoter region following NGF withdrawal. Collectively, these findings support a mechanism in which NGF deprivation, Akt dephosphorylation/inactivation, FoxO dephosphorylation/activation and Trib3 induction are linked in a self-amplifying feed-forward loop that culminates in neuron death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.