ArticleCell death and differentiation2013
Trim17-mediated ubiquitination and degradation of Mcl-1 initiate apoptosis in 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 62 papers.
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Who cites it
62 citing papers in PubMed, 102 citations in OpenAlex.
- TRIM17 downregulation modulates CRPC progression and enzalutamide resistance by derepressing BCL2 expression via the p53-dependent and p53-independent pathways.Cell death and differentiation · 2026Article
- GET3 regulates apoptosis via tail-anchoring of MCL1.Cell death and differentiation · 2026Article
- TRIM17 promotes the progression of osteosarcoma by regulating PDK1 m6A modification-mediated AKT/mTOR pathway activation through ubiquitination of FTO.Cell death & disease · 2025Article
- Cul5bioRxiv : the preprint server for biology · 2025Article
- A new era in cancer therapy: targeting the Proteasome-Bcl-2 axis.Journal of experimental & clinical cancer research : CR · 2025Review
- Impact of LITAF on Mitophagy and Neuronal Damage in Epilepsy via MCL-1 Ubiquitination.CNS neuroscience & therapeutics · 2025Article
- E3 ubiquitin ligase TRIM31 alleviates dopaminergic neurodegeneration by promoting proteasomal degradation of VDAC1 in Parkinson's Disease model.Cell death and differentiation · 2024Article
- Review
- Phosphoproteomic analysis reveals changes in A-Raf-related protein phosphorylation in response to Toxoplasma gondii infection in porcine macrophages.Parasites & vectors · 2024Article
- Cerebellum and Aging: Update and Challenges.Aging and disease · 2024Review
- Multipronged regulation of autophagy and apoptosis: emerging role of TRIM proteins.Cellular & molecular biology letters · 2024Review
- TRIM17-mediated ubiquitination and degradation of RBM38 promotes cisplatin resistance in non-small cell lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- The E3 ubiquitin ligase TRIM17 promotes gastric cancer survival and progression via controlling BAX stability and antagonizing apoptosis.Cell death and differentiation · 2023Article
- MARCH5 regulates mitotic apoptosis through MCL1-dependent and independent mechanisms.Cell death and differentiation · 2023Article
- The roles of E3 ubiquitin ligases in cancer progression and targeted therapy.Clinical and translational medicine · 2023Review
- Mechanisms of MCL-1 Protein Stability Induced by MCL-1 Antagonists in B-Cell Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Trim39 regulates neuronal apoptosis by acting as a SUMO-targeted E3 ubiquitin-ligase for the transcription factor NFATc3.Cell death and differentiation · 2022Article
- TRIM family proteins: roles in proteostasis and neurodegenerative diseases.Open biology · 2022Review
- Keeping Cell Death Alive: An Introduction into the French Cell Death Research Network.Biomolecules · 2022Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Short-term proteasome inhibition has been shown to prevent neuronal apoptosis. However, the key pro-survival proteins that must be degraded for triggering neuronal death are mostly unknown. Here, we show that Mcl-1, an anti-apoptotic Bcl-2 family member, is degraded by the proteasome during neuronal apoptosis. Using primary cultures of cerebellar granule neurons deprived of serum and KCl, we found that ubiquitination and proteasomal degradation of Mcl-1 depended on its prior phosphorylation by GSK3, providing the first insight into post-translational regulation of Mcl-1 in neurons. In a previous study, we have reported that the E3 ubiquitin-ligase Trim17 is both necessary and sufficient for neuronal apoptosis. Here, we identified Trim17 as a novel E3 ubiquitin-ligase for Mcl-1. Indeed, Trim17 co-immunoprecipitated with Mcl-1. Trim17 ubiquitinated Mcl-1 in vitro. Overexpression of Trim17 decreased the protein level of Mcl-1 in a phosphorylation- and proteasome-dependent manner. Finally, knock down of Trim17 expression reduced both ubiquitination and degradation of Mcl-1 in neurons. Moreover, impairment of Mcl-1 phosphorylation, by kinase inhibition or point mutations, not only decreased ubiquitination and degradation of Mcl-1, but also blocked the physical interaction between Trim17 and Mcl-1. As this stabilization of Mcl-1 increased its neuroprotective effect, our data strongly suggest that Trim17-mediated ubiquitination and degradation of Mcl-1 is necessary for initiating neuronal death.
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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.