ArticleThe Journal of biological chemistry2009
Inhibiting the calcineurin-NFAT (nuclear factor of activated T cells) signaling pathway with a regulator of calcineurin-derived peptide without affecting general calcineurin phosphatase activity.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 64 citations in OpenAlex.
- Pharmacological strategies for mitigating anti-TNF biologic immunogenicity in rheumatoid arthritis patients.Current opinion in pharmacology · 2023Review
- Targeting CaN/NFAT in Alzheimer's brain degeneration.Frontiers in immunology · 2023Review
- The Overexpression of miR-377 Aggravates Sepsis-Induced Myocardial Hypertrophy by Binding to Rcan2 and Mediating CaN Activity.Oxidative medicine and cellular longevity · 2022Article
- Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats.International journal of molecular medicine · 2021Article
- Q134R: Small chemical compound with NFAT inhibitory properties improves behavioral performance and synapse function in mouse models of amyloid pathology.Aging cell · 2021Article
- The structure of the RCAN1:CN complex explains the inhibition of and substrate recruitment by calcineurin.Science advances · 2020Article
- A novel peptide exerts potent immunosuppression by blocking the two-site interaction of NFAT with calcineurin.The Journal of biological chemistry · 2020Article
- ILC3-derived OX40L is essential for homeostasis of intestinal Tregs in immunodeficient mice.Cellular & molecular immunology · 2020Article
- Quantitative mapping of protein-peptide affinity landscapes using spectrally encoded beads.eLife · 2019Article
- Pathogenesis of Skin Injury of Systemic Lupus Erythematosus.Current rheumatology reports · 2018Review
- Amphotericin B, an Anti-Fungal Medication, Directly Increases the Cytotoxicity of NK Cells.International journal of molecular sciences · 2017Article
- RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice.Scientific reports · 2017Article
- Epigenetics and Vasculitis: a Comprehensive Review.Clinical reviews in allergy & immunology · 2016Review
- Twenty years after ACEIs and ARBs: emerging treatment strategies for diabetic nephropathy.American journal of physiology. Renal physiology · 2015Review
- Pathogenesis and targeted treatment of skin injury in SLE.Nature reviews. Rheumatology · 2015Review
- Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization.PloS one · 2015Article
- Identification and mutational analyses of phosphorylation sites of the calcineurin-binding protein CbpA and the identification of domains required for calcineurin binding in Aspergillus fumigatus.Frontiers in microbiology · 2015Article
- The vertebrate RCAN gene family: novel insights into evolution, structure and regulation.PloS one · 2014Article
- Small molecules in the treatment of systemic lupus erythematosus.Clinical immunology (Orlando, Fla.) · 2013Review
- Regulator of calcineurin 1 (Rcan1) has a protective role in brain ischemia/reperfusion injury.Journal of neuroinflammation · 2012Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calcineurin phosphatase plays a crucial role in T cell activation. Dephosphorylation of the nuclear factors of activated T cells (NFATs) by calcineurin is essential for activating cytokine gene expression and, consequently, the immune response. Current immunosuppressive protocols are based mainly on calcineurin inhibitors, cyclosporine A and FK506. Unfortunately, these drugs are associated with severe side effects. Therefore, immunosuppressive agents with higher selectivity and lower toxicity must be identified. The immunosuppressive role of the family of proteins regulators of calcineurin (RCAN, formerly known as DSCR1) which regulate the calcineurin-NFAT signaling pathway, has been described recently. Here, we identify and characterize the minimal RCAN sequence responsible for the inhibition of calcineurin-NFAT signaling in vivo. The RCAN-derived peptide spanning this sequence binds to calcineurin with high affinity. This interaction is competed by a peptide spanning the NFAT PXIXIT sequence, which binds to calcineurin and facilitates NFAT dephosphorylation and activation. Interestingly, the RCAN-derived peptide does not inhibit general calcineurin phosphatase activity, which suggests that it may have a specific immunosuppressive effect on the calcineurin-NFAT signaling pathway. As such, the RCAN-derived peptide could either be considered a highly selective immunosuppressive compound by itself or be used as a new tool for identifying innovative immunosuppressive agents. We developed a low throughput assay, based on the RCAN1-calcineurin interaction, which identifies dipyridamole as an efficient in vivo inhibitor of the calcineurin-NFAT pathway that does not affect calcineurin phosphatase activity.
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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.