ArticleMolecular immunology2010
Proximal human FOXP3 promoter transactivated by NF-kappaB and negatively controlled by feedback loop and SP3.
Article in Molecular immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Novel non-coding FOXP3 transcript isoform associated to potential transcriptional interference in human regulatory T cells.RNA biology · 2025Article
- Article
- Toxoplasma gondii excreted-secreted antigens suppress Foxp3 promoter activity via a SP1-dependent mechanism.Journal of cellular and molecular medicine · 2020Article
- Extracellular Purine Metabolism Is the Switchboard of Immunosuppressive Macrophages and a Novel Target to Treat Diseases With Macrophage Imbalances.Frontiers in immunology · 2018Article
- Tbet is a critical modulator of FoxP3 expression in autoimmune graft-Haematologica · 2017Article
- Regulation of UNC-130/FOXD-mediated mesodermal patterning in C. elegans.Developmental biology · 2016Article
- Article
- The Treg-specific demethylated region stabilizes Foxp3 expression independently of NF-κB signaling.PloS one · 2014Article
- IL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients.The Journal of clinical investigation · 2014Article
- Gene therapy-mediated reprogramming tumor infiltrating T cells using IL-2 and inhibiting NF-κB signaling improves the efficacy of immunotherapy in a brain cancer model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2012Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Forkhead box protein 3 (Foxp3) is indispensable for the development of CD4(+)CD25(+) regulatory T cells (Tregs). Here we analyzed three prominent evolutionary conserved regions (ECRs) upstream of the transcription start site of the human FOXP3 gene. We show that ECR2 and ECR3 fragments derived from positions -1.3 to -2.0 kb and -5.0 to -6.0 kb, respectively, display basal transcriptional activity. Reporter constructs derived from ECR1, located between -0.6 and +0.23 kb and thus the most proximal ECR in respect of transcription initiation, remained almost inactive. However, ECR1 was transactivated by the NF-kappaB subunit p65 in HEK 293 cells. In Jurkat and primary T cells, in addition to p65, a second stimulus delivered by either T-cell receptor stimulation or addition of PMA was needed. Co-expression of I kappaB alpha inhibited p65-mediated FOXP3 proximal promoter transactivation, and the NF-kappaB inhibitor curcumin reduced Foxp3 neoexpression in IL-2/CD3/CD28/TGF-beta stimulated PBMCs. Moreover, proximal FOXP3 promoter transactivation was inhibited by Foxp3 and the SP transcription factor family member SP3. Thus, the human proximal FOXP3 promoter is controlled by activation through the TCR involving PKC and the NF-kappaB subunit p65 and by inhibition through a negative feedback loop and SP3.
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