ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Egr-1 transactivates Bim gene expression to promote neuronal apoptosis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 80 citations in OpenAlex.
- Low-dose nicotine enhances arecoline-induced human oral mucosa fibroblast proliferation by stabilizing Egr-1 protein.Odontology · 2026Article
- Genetic Anatomy and Ontogenetic Roles of Early Growth Response 1 (Egr1) in Human and Mouse.Development & reproduction · 2026Review
- Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health.Nature communications · 2025Article
- Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype.NPJ Parkinson's disease · 2025Article
- Machine learning identifies potential diagnostic biomarkers associated with ferroptosis in obstructive sleep apnea.Experimental and therapeutic medicine · 2025Article
- The impact of chronic intermittent hypoxia on enzymatic activity in memory-associated brain regions of male and female rats.Biology of sex differences · 2025Article
- The impact of chronic intermittent hypoxia on enzymatic activity in memory-associated brain regions of male and female rats.Research square · 2024Article
- Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.bioRxiv : the preprint server for biology · 2024Article
- Loss of DJ-1 function contributes to Parkinson's disease pathogenesis in mice via RACK1-mediated PKC activation and MAO-B upregulation.Acta pharmacologica Sinica · 2023Article
- Induction of filopodia formation by α-Actinin-2 via RelA with a feedforward activation loop promoting overt bone marrow metastasis of gastric cancer.Journal of translational medicine · 2023Article
- microRNA-221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease.Brain and behavior · 2023Article
- Glucose Homeostasis and Pancreatic Islet Size Are Regulated by the Transcription Factors Elk-1 and Egr-1 and the Protein Phosphatase Calcineurin.International journal of molecular sciences · 2023Review
- GPR43 activation-mediated lipotoxicity contributes to podocyte injury in diabetic nephropathy by modulating the ERK/EGR1 pathway.International journal of biological sciences · 2022Article
- EGR1 Addiction in Diffuse Large B-cell Lymphoma.Molecular cancer research : MCR · 2021Article
- Identification of Molecular Network Associated with Neuroprotective Effects of Yashtimadhu (ACS omega · 2020Article
- Ischemia/hypoxia inhibits cardiomyocyte autophagy and promotes apoptosis via the Egr-1/Bim/Beclin-1 pathway.Journal of geriatric cardiology : JGC · 2020Article
- Early Growth Response 1 Deficiency Protects the Host against Pseudomonas aeruginosa Lung Infection.Infection and immunity · 2019Article
- Cathepsin L induced PC-12 cell apoptosis via activation of B-Myb and regulation of cell cycle proteins.Acta pharmacologica Sinica · 2019Article
- Podocyte histone deacetylase activity regulates murine and human glomerular diseases.The Journal of clinical investigation · 2019Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proapoptotic BH3-only protein Bim is a crucial regulator of neuronal apoptosis. Previous studies have indicated the involvement of the c-Jun, FOXO1/3a, and B/C-Myb transcription factors in the regulation of Bim during neuronal apoptosis. However, the mechanism underlying the transcriptional regulation of Bim in activity deprivation-induced neuronal apoptosis has remained unclear. The present study demonstrates that early growth response 1 (Egr-1), rather than c-Jun, FOXO1/3a, or B/C-Myb, directly transactivates Bim gene expression to mediate apoptosis of rat cerebellar granule neurons. We showed that Egr-1 was sufficient and necessary for neuronal apoptosis. Suppression of Egr-1 activity using dominant-negative mutant or knockdown of Egr-1 using small interfering RNAs led to a decrease in Bim expression, whereas overexpression of Egr-1 resulted in induction of Bim. Deletion and site-directed mutagenesis of the Bim promoter revealed that Bim transcriptional activation depends primarily on a putative Egr-binding sequence between nucleotides -56 and -47 upstream of the start site. We also showed that Egr-1 binding to this sequence increased in response to activity deprivation in vitro and in vivo. Moreover, inhibition of Egr-1 binding to the Bim promoter, by mithramycin A and chromomycin A3, reduced the activity deprivation-induced increases in Bim promoter activity and mRNA and protein levels and protected neurons from apoptosis, further supporting the Egr-1-mediated transactivation of Bim. Additionally, Bim overcame the Egr-1 knockdown-mediated inhibition of apoptosis, whereas Bim knockdown impaired the increase in apoptosis induced by Egr-1. These findings establish Bim as an Egr-1 target gene in neurons, uncovering a novel Egr-1/Bim pathway by which activity deprivation induces neuronal apoptosis.
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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.