ArticleBiochimica et biophysica acta. Molecular cell research2019
Induction of early growth response gene 1 (EGR1) by endoplasmic reticulum stress is mediated by the extracellular regulated kinase (ERK) arm of the MAPK pathways.
Article in Biochimica et biophysica acta. Molecular cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- Shock Induced Endotheliopathy and High Trauma Mortality-Fight-or-Flight Response Revisited.International journal of molecular sciences · 2026Review
- Perturb-seq reveals TCF7 as a transcriptional link between MAPK- and Wnt-driven gene expression.Nucleic acids research · 2026Article
- Multi-omics network reconstruction with collaborative graphical lasso.Bioinformatics (Oxford, England) · 2026Article
- Antiviral effect of chelerythrine chloride against tick-borne encephalitis virus.Virology journal · 2026Article
- Genetic Anatomy and Ontogenetic Roles of Early Growth Response 1 (Egr1) in Human and Mouse.Development & reproduction · 2026Review
- EGR1 Nuclear Condensates Promote Renal Cyst Development in Polycystic Kidney Disease.Exploration (Beijing, China) · 2026Article
- Platelet-derived growth factor receptor alpha regulates fetal testis differentiation via an ERK-CREB axis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Hypoxia-induced EGR1 remodels neutrophils to suppress antitumor immunity.Science immunology · 2025Article
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- Restoration of LAT activity improves CAR T cell sensitivity and persistence in response to antigen-low acute lymphoblastic leukemia.Cancer cell · 2025Article
- The Yeast-Fermented Garlic and a Balance of Spermine/Spermidine Activates Autophagy via EGR1 Transcriptional Factor.Molecular nutrition & food research · 2025Article
- EGR1 regulates oral epithelial cell responses toVirulence · 2024Article
- Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation.Biomolecules · 2024Article
- Identification of PPREs and PPRE associated genes in the human genome: insights into related kinases and disease implications.Frontiers in immunology · 2024Article
- Conditioned Medium Derived From Human Dental Follicle Mesenchymal Stem Cells Alleviates Macrophage Proinflammatory Responses Through MAPK-ERK-EGR1 Axis.Stem cells international · 2024Article
- Effects of lysine and methionine on mRNA expression of candidate transcription factors by primary bovine mammary epithelial cells.PloS one · 2024Article
- Transcriptome Profiling of Cardiac Glycoside Treatment Reveals EGR1 and Downstream Proteins of MAPK/ERK Signaling Pathway in Human Breast Cancer Cells.International journal of molecular sciences · 2023Article
- RBM25 regulates hypoxic cardiomyocyte apoptosis through CHOP-associated endoplasmic reticulum stress.Cell stress & chaperones · 2023Article
- NFκB pathway dysregulation due to reduced RelB expression leads to severe autoimmune disorders and declining immunity.Journal of autoimmunity · 2023Article
- EGR1 drives cell proliferation by directly stimulating TFEB transcription in response to starvation.PLoS biology · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress activates three principal signaling pathways, collectively known as the unfolded protein response, leading to translational and transcriptional control mechanisms that dictate the cell's response as adaptive or apoptotic. The present study illustrates that for HepG2 human hepatocellular carcinoma cells the signaling pathways triggered by ER stress extend beyond the three principal pathways to include mitogen-activated protein kinase (MAPK) signaling, leading to activation of transcription from the early growth response 1 (EGR1) gene. Analysis provided evidence for a SRC-RAS-RAF-MEK-ERK cascade mechanism that leads to enhanced phosphorylation of the transcription factor ELK1. ELK1 and serum response factor (SRF) are constitutively bound to the EGR1 promoter and are phosphorylated by nuclear localized ERK. The promoter abundance of both phospho-SRF and phopsho-ELK1 was increased by ER stress, but the SRF phosphorylation was transient. Knockdown of ELK1 had little effect on the basal EGR1 mRNA content, but completely blocked the increase in response to ER stress. Conversely, knockdown of SRF suppressed basal EGR1 mRNA content, but had only a small effect on the induction by ER stress. This research highlights the importance of MAPK signaling in response to ER stress and identifies ELK1 as a transcriptional mediator and the EGR1 gene as a target.
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