ArticleThe Journal of experimental medicine1994
Interleukin 2 transcription factors as molecular targets of cAMP inhibition: delayed inhibition kinetics and combinatorial transcription roles.
Article in The Journal of experimental medicine, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 163 citations in OpenAlex.
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- Modulation of intracellular calcium signaling by microRNA-34a-5p.Cell death & disease · 2018Article
- Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells.Respiratory research · 2016Article
- Transmembrane TNF-TNFR2 Impairs Th17 Differentiation by Promoting Il2 Expression.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Inhibition of Gαs/cAMP Signaling Decreases TCR-Stimulated IL-2 transcription in CD4(+) T Helper Cells.Journal of molecular signaling · 2015Article
- T-cell identity and epigenetic memory.Current topics in microbiology and immunology · 2012Review
- Cyclic AMP: a selective modulator of NF-κB action.Cellular and molecular life sciences : CMLS · 2011Review
- Two-step binding of transcription factors causes sequential chromatin structural changes at the activated IL-2 promoter.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Multilayered specification of the T-cell lineage fate.Immunological reviews · 2010Review
- Prostaglandin E2 regulates B cell proliferation through a candidate tumor suppressor, Ptger4.The Journal of experimental medicine · 2008Article
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- Multiple cAMP-induced signaling cascades regulate prolactin expression in T cells.Cellular and molecular life sciences : CMLS · 2006Article
- Cell-type-specific epigenetic marking of the IL2 gene at a distal cis-regulatory region in competent, nontranscribing T-cells.Nucleic acids research · 2005Article
- The quantal theory of how the immune system discriminates between "self and non-self"Medical immunology (London, England) · 2004Article
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- Immunological mechanisms in specific immunotherapy.Springer seminars in immunopathology · 2004Review
- Transcriptional activation of the interleukin-2 promoter by hepatitis C virus core protein.Journal of virology · 2001Article
- Renal cell carcinoma-derived gangliosides suppress nuclear factor-kappaB activation in T cells.The Journal of clinical investigation · 1999Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Elevation of cAMP can cause gene-specific inhibition of interleukin 2 (IL-2) expression. To investigate the mechanism of this effect, we have combined electrophoretic mobility shift assays and in vivo genomic footprinting to assess both the availability of putative IL-2 transcription factors in forskolin-treated cells and the functional capacity of these factors to engage their sites in vivo. All observed effects of forskolin depended upon protein kinase A, for they were blocked by introduction of a dominant negative mutant subunit of protein kinase A. In the EL4.E1 cell line, we report specific inhibitory effects of cAMP elevation both on NF-kappa B/Rel family factors binding at -200 bp, and on a novel, biochemically distinct "TGGGC" factor binding at -225 bp with respect to the IL-2 transcriptional start site. Neither NF-AT nor AP-1 binding activities are detectably inhibited in gel mobility shift assays. Elevation of cAMP inhibits NF-kappa B activity with delayed kinetics in association with a delayed inhibition of IL-2 RNA accumulation. Activation of cells in the presence of forskolin prevents the maintenance of stable protein-DNA interactions in vivo, not only at the NF-kappa B and TGGGC sites of the IL-2 enhancer, but also at the NF-AT, AP-1, and other sites. This result, and similar results in cyclosporin A-treated cells, imply that individual IL-2 transcription factors cannot stably bind their target sequences in vivo without coengagement of all other distinct factors at neighboring sites. It is proposed that nonhierarchical, cooperative enhancement of binding is a structural basis of combinatorial transcription factor action at the IL-2 locus.
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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.