ArticleBMC neuroscience2011
The MEK-ERK pathway negatively regulates bim expression through the 3' UTR in sympathetic neurons.
Article in BMC neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Trial
- Multi-Omic Analysis of CIC's Functional Networks Reveals Novel Interaction Partners and a Potential Role in Mitotic Fidelity.Cancers · 2023Article
- Anti-Apoptotic Effects of Carotenoids in Neurodegeneration.Molecules (Basel, Switzerland) · 2020Review
- Oncogenic K-Ras4B Dimerization Enhances Downstream Mitogen-activated Protein Kinase Signaling.Journal of molecular biology · 2020Article
- Silymarin and its active component silibinin act as novel therapeutic alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling cascade.Cellular oncology (Dordrecht, Netherlands) · 2017Article
- Regulatory region genetic variation is associated with FYN expression in Alzheimer's disease.Neurobiology of aging · 2017Article
- Sensitivity of GBM cells to cAMP agonist-mediated apoptosis correlates with CD44 expression and agonist resistance with MAPK signaling.Cell death & disease · 2016Article
- BCR-signaling-induced cell death demonstrates dependency on multiple BH3-only proteins in a murine model of B-cell lymphoma.Cell death and differentiation · 2016Article
- Targeting ERK1/2-bim signaling cascades by BH3-mimetic ABT-737 as an alternative therapeutic strategy for oral cancer.Oncotarget · 2015Article
- Interferon gamma induces protective non-canonical signaling pathways in primary neurons.Journal of neurochemistry · 2015Article
- [Effect and significance of BH3-only protein in targeted therapy of non-small cell lung cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2014Review
- Programmed cell death during neuronal development: the sympathetic neuron model.Cell death and differentiation · 2014Review
- Receptor tyrosine kinase (RTK) signalling in the control of neural stem and progenitor cell (NSPC) development.Molecular neurobiology · 2014Review
- Article
- JNK3 involvement in nerve cell apoptosis and neurofunctional recovery after traumatic brain injury.Neural regeneration research · 2013Article
- MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small-cell lung cancer through BIM down-regulation.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Cyclic AMP regulates formation of mammary epithelial acini in vitro.Molecular biology of the cell · 2012Article
- Alternative splicing of Bim and Erk-mediated Bim(EL) phosphorylation are dispensable for hematopoietic homeostasis in vivo.Cell death and differentiation · 2012Article
- ER stress in retinal degeneration in S334ter Rho rats.PloS one · 2012Article
- Global analysis of gene expression in NGF-deprived sympathetic neurons identifies molecular pathways associated with cell death.BMC genomics · 2011Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundApoptosis plays a critical role during neuronal development and disease. Developing sympathetic neurons depend on nerve growth factor (NGF) for survival during the late embryonic and early postnatal period and die by apoptosis in its absence. The proapoptotic BH3-only protein Bim increases in level after NGF withdrawal and is required for NGF withdrawal-induced death. The regulation of Bim expression in neurons is complex and this study describes a new mechanism by which an NGF-activated signalling pathway regulates bim gene expression in sympathetic neurons.
resultsWe report that U0126, an inhibitor of the prosurvival MEK-ERK pathway, increases bim mRNA levels in sympathetic neurons in the presence of NGF. We find that this effect is independent of PI3-K-Akt and JNK-c-Jun signalling and is not mediated by the promoter, first exon or first intron of the bim gene. By performing 3' RACE and microinjection experiments with a new bim-LUC+3'UTR reporter construct, we show that U0126 increases bim expression via the bim 3' UTR. We demonstrate that this effect does not involve a change in bim mRNA stability and by using PD184352, a specific MEK1/2-ERK1/2 inhibitor, we show that this mechanism involves the MEK1/2-ERK1/2 pathway. Finally, we demonstrate that inhibition of MEK/ERK signalling independently reduces cell survival in NGF-treated sympathetic neurons.
conclusionsThese results suggest that in sympathetic neurons, MEK-ERK signalling negatively regulates bim expression via the 3' UTR and that this regulation is likely to be at the level of transcription. This data provides further insight into the different mechanisms by which survival signalling pathways regulate bim expression in neurons.
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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.