ArticleThe Journal of biological chemistry2011
Identification of a novel Bcl-2-interacting mediator of cell death (Bim) E3 ligase, tripartite motif-containing protein 2 (TRIM2), and its role in rapid ischemic tolerance-induced neuroprotection.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
- Neuroprotective Role of E3 Ubiquitin Ligase TRIM2 in Parkinson's Disease: Attenuation of Oxidative Stress and Apoptosis via Promoting ELAVL1 Ubiquitination.CNS neuroscience & therapeutics · 2026Article
- Early, sex-dependent and progressive proteomic imbalance in the amygdala during Alzheimer´s disease continuum.Biology of sex differences · 2026Article
- Integrated multi-omics analysis and functional validation reveal the role of TRIM2 as a potential novel biomarker in breast cancer.Breast cancer research : BCR · 2026Article
- TRIM2 E3 ligase substrate discovery reveals zinc-mediated regulation of TMEM106B in the endolysosomal pathway.EMBO reports · 2026Article
- TRIM2 suppresses prostate cancer progression by promoting ubiquitin-mediated degradation of DTNBP1.Frontiers in molecular biosciences · 2026Article
- Cul5bioRxiv : the preprint server for biology · 2025Article
- TRIM2 inhibits apoptosis by ubiquitinating BNIP3 to protect the intestine against ischemia-reperfusion injury in mice.Communications biology · 2025Article
- Review
- TRIM2: a double-edged sword preventing apoptosis.The FEBS journal · 2025Article
- Mechanistic exploration of ubiquitination-mediated pathways in cerebral ischemic injury.Molecular biology reports · 2024Review
- Tripartite motif 2b (Journal of virology · 2024Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Divergent self-association properties of paralogous proteins TRIM2 and TRIM3 regulate their E3 ligase activity.Nature communications · 2022Article
- The role of Ubiquitination in Apoptosis and Necroptosis.Cell death and differentiation · 2022Review
- Expression and Role of TRIM2 in Human Diseases.BioMed research international · 2022Review
- Oncogenic function of TRIM2 in pancreatic cancer by activating ROS-related NRF2/ITGB7/FAK axis.Oncogene · 2020Observational
- Exploring Neuronal Vulnerability to Head Trauma Using a Whole Exome Approach.Journal of neurotrauma · 2020Article
- Article
- A recessive Trim2 mutation causes an axonal neuropathy in mice.Neurobiology of disease · 2020Article
- Cathepsin K inhibition-induced mitochondrial ROS enhances sensitivity of cancer cells to anti-cancer drugs through USP27x-mediated Bim protein stabilization.Redox biology · 2020Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
We have previously shown that the cell death-promoting protein Bcl-2-interacting mediator of cell death (Bim) is ubiquitinated and degraded following a neuroprotection-conferring episode of brief ischemia (preconditioning). Here, we identify the E3 ligase that ubiquitinates Bim in this model, using a proteomics approach. Using phosphorylated GST-Bim as bait, we precipitated and identified by mass spectrometry tripartite motif protein 2 (TRIM2), a RING (really interesting new gene) domain-containing protein. The reaction between TRIM2 and Bim was confirmed using co-immunoprecipitation followed by immunoblotting. We show that TRIM2 binds to Bim when it is phosphorylated by p42/p44 MAPK but does not interact with a nonphosphorylatable Bim mutant (3ABim). 12-O-tetradecanoylphorbol-13-acetate activation of p42/p44 MAPK drives Bim ubiquitination in mouse embryonic fibroblast cells and is associated with an increased interaction between TRIM2 and Bim. One hour following preconditioning ischemia, the binding of Bim to TRIM2 increased, consistent with the time window of enhanced Bim degradation. Blocking p42/p44 MAPK activation following preconditioning ischemia with U0126 or using the nonphosphorylatable 3ABim reduced the binding between Bim and TRIM2. Immunodepletion of TRIM2 from cell lysates prepared from preconditioned cells reduced Bim ubiquitination. Finally, suppression of TRIM2 expression, using lentivirus transduction of shRNAmir, stabilized Bim protein levels and blocked neuroprotection observed in rapid ischemic tolerance. Taken together, these data support a role for TRIM2 in mediating the p42/p44 MAPK-dependent ubiquitination of Bim in rapid ischemic tolerance.
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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.