ArticleNucleic acids research2003
Early growth response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression.
Article in Nucleic acids research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 145 citations in OpenAlex.
- Two Faces of NFAT Transcription Factors in LymphocytesBiomolecules · 2026Review
- A Comprehensive Bibliometric and Visual Analysis of EGR1 in Cardiovascular Disease.Molecular biotechnology · 2026Review
- Myeloid EGR1 contributes to Th17/Treg imbalance during acute liver allograft rejection in a rat model.Frontiers in immunology · 2026Article
- Multifaceted regulatory mechanisms of the EGR family in tumours and prospects for therapeutic applications (Review).International journal of molecular medicine · 2025Review
- Non-canonical Wnt signaling pathway activated NFATC3 promotes GDF15 expression in MASH: prospective analyses of UK biobank proteomic data.Hepatology international · 2025Article
- Single cell transcriptome sequencing indicates the cellular heterogeneity of small intestine tissue in celiac disease.Scientific reports · 2025Article
- Early Growth Response Factor 4 (EGR4) Expression in Gut Tissues and Regional Lymph Nodes of Cattle with Different Types of Paratuberculosis-Associated Lesions: Potential Role of EGR4 in Resilience to Paratuberculosis.Animals : an open access journal from MDPI · 2025Article
- Double-negative T cells with a distinct transcriptomic profile are abundant in the peripheral blood of patients with breast cancer.Breast cancer research and treatment · 2025Article
- Exploring the genome-wide transcriptomic responses of Bulinus truncatus to Schistosoma haematobium infection: An important host-parasite system involved in the transmission of human urogenital schistosomiasis.Molecular immunology · 2024Article
- IL-33 priming and antigenic stimulation synergistically promote the transcription of proinflammatory cytokine and chemokine genes in human skin mast cells.BMC genomics · 2023Article
- Early growth response-1: Key mediators of cell death and novel targets for cardiovascular disease therapy.Frontiers in cardiovascular medicine · 2023Review
- EGR1 Upregulation during Encephalitic Viral Infections Contributes to Inflammation and Cell Death.Viruses · 2022Article
- NUAK2 and RCan2 participate in the p53 mutant pro-tumorigenic network.Biology direct · 2021Article
- Application of specialized pro-resolving mediators in periodontitis and peri-implantitis: a review.European journal of oral sciences · 2021Review
- Early Growth Response 1 Suppresses Macrophage Phagocytosis by Inhibiting NRF2 Activation Through Upregulation of Autophagy DuringFrontiers in cellular and infection microbiology · 2021Article
- Loss of EGR3 is an independent risk factor for metastatic progression in prostate cancer.Oncogene · 2020Article
- Class IA PI3K regulatory subunits: p110-independent roles and structures.Biochemical Society transactions · 2020Review
- Cardiac resynchronization therapy reduces expression of inflammation-promoting genes related to interleukin-1β in heart failure.Cardiovascular research · 2020Article
- Stress genomics revisited: gene co-expression analysis identifies molecular signatures associated with childhood adversity.Translational psychiatry · 2020Article
- Early Growth Response 1 Deficiency Protects the Host against Pseudomonas aeruginosa Lung Infection.Infection and immunity · 2019Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of transcription factors by receptor mediated signaling is an essential step for T lymphocyte effector function. Following antigenic stimulation of T cells the two central cytokines IL-2 and TNFalpha are co-expressed and co-regulated. Two important transcription factors, i.e., early growth response (EGR) protein EGR-1 and nuclear factors of activated T cells (NFAT) protein NFATc, regulate transcription of the human IL-2 cytokine and the same combination of EGR and NFAT proteins seems relevant for coordinated cytokine expression. Here we demonstrate that the zinc finger protein EGR-1 and two members of the NFAT protein family bind simultaneously to adjacent elements position -168 to -150 within the TNFalpha promoter. Both promoter sites are important for TNFalpha gene transcription as shown by transfection assays having the IL-2 and TNFalpha promoters linked to a luciferase reporter. The use of promoter deletion constructs with the zinc finger protein (ZIP), the NFAT binding element or a combination of both deleted show a functional cooperation of these elements and of their binding factors. These experiments demonstrate that EGR-1 as well as EGR-4 functionally cooperate with NFAT proteins and induce expression of both cytokine genes. Using tagged NFATc and NFATp in glutathione S-transferase pull down assays showed interaction and physical complex formation of each NFAT protein with recombinant, as well as native, EGR-1 and EGR-4 proteins. Thus EGR-NFAT interaction and complex formation seems essential for human cytokine expression as adjacent ZIP and NFAT elements are conserved in the IL-2 and TNFalpha gene promoters. Binding of regulatory EGR and NFAT factors to these sites and the functional interaction and formation of stable heterodimeric complexes indicate an important role of these factors for gene transcription.
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Registered trials
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.