ArticleThe EMBO journal1994
Calcineurin acts in synergy with PMA to inactivate I kappa B/MAD3, an inhibitor of NF-kappa B.
Article in The EMBO journal, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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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
92 citing papers in PubMed, 332 citations in OpenAlex.
- Mechanisms of rapid induction of interleukin-22 in activated T cells and its modulation by cyclosporin a.The Journal of biological chemistry · 2012Trial
- Autonomous Oscillations of NF-κB.Advances in experimental medicine and biology · 2026Review
- From bench to bed: deep insights the tacrolimus-induced diabetes and gut microbiota dysbiosis.European journal of medical research · 2025Review
- Mechanism of tacrolimus in the treatment of lupus nephritis.Frontiers in pharmacology · 2024Review
- Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells.iScience · 2022Article
- The pathogenesis of prevalent aerobic bacteria in aerobic vaginitis and adverse pregnancy outcomes: a narrative review.Reproductive health · 2022Review
- Calcineurin Aα Contributes to IgE-Dependent Mast-Cell Mediator Secretion in Allergic Inflammation.Journal of innate immunity · 2022Article
- A Review of Calcineurin Biophysics with Implications for Cardiac Physiology.International journal of molecular sciences · 2021Review
- Aplastic anemia in a patient with CVID due to NFKB1 haploinsufficiency.Cold Spring Harbor molecular case studies · 2020Article
- Ethnobotany, Phytochemistry and Pharmacological Activity ofPlants (Basel, Switzerland) · 2020Review
- BCR-Induced CaCell reports · 2020Article
- Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes.Journal of leukocyte biology · 2020Article
- Mycophenolate mofetil, azathioprine and tacrolimus: mechanisms in rheumatology.Nature reviews. Rheumatology · 2020Review
- CaAdvances in cancer research · 2020Review
- Anti-Inflammatory Properties ofMolecules (Basel, Switzerland) · 2019Article
- STIM- and Orai-mediated calcium entry controls NF-κB activity and function in lymphocytes.Cell calcium · 2018Review
- Regulator of calcineurin 1 differentially regulates TLR-dependent MyD88 and TRIF signaling pathways.PloS one · 2018Article
- Human NF-κB1 Haploinsufficiency and Epstein-Barr Virus-Induced Disease-Molecular Mechanisms and Consequences.Frontiers in immunology · 2017Review
- Review
- Charged MVB protein 5 is involved in T-cell receptor signaling.Experimental & molecular medicine · 2016Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interleukin-2 (IL-2) promoter consists of several independent T cell receptor (TcR) responsive elements. The induction of promoters dependent on these elements is inhibitable by the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK-506). Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is the FK-506- and CsA-sensitive enzyme required for TcR mediated activation of the IL-2 promoter. We report that a constitutively active form of calcineurin partially substitutes for the Ca2+ co-stimulus required to activate the IL-2 promoter elements IL-2A (which binds the factors OAP and Oct-1) and IL-2E (which binds NF-AT), and completely substitutes for the Ca2+ co-stimulus required to stimulate an NF-kappa B-dependent element. Calcineurin stimulates the NF-kappa B element by enhancing inactivation of I kappa B/MAD3, an inhibitor of NF-kappa B, thereby increasing the amount of nuclear NF-kappa B DNA binding activity. These data provide the first demonstration in vivo that activation of a protein phosphatase can inactivate I kappa B, and suggest one possible explanation for mechanism-based toxicities associated with FK-506 and CsA by demonstrating that these drugs can inhibit the calcineurin-dependent activation of a virtually ubiquitous transcription factor.
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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.