ArticleScience advances2020
The structure of the RCAN1:CN complex explains the inhibition of and substrate recruitment by calcineurin.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- A multivalent docking platform and Rcn1-mediated inhibition control the extent of calcineurin recruitment to the cell division site for the dephosphorylation of multiple cytokinetic proteins.bioRxiv : the preprint server for biology · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- The clinical missense variant E282K in PPP3CA/calcineurin shifts substrate dephosphorylation by altering active site recruitment.Nature communications · 2026Article
- Fuzziness in enzymatic catalysis.Current opinion in structural biology · 2025Review
- RCAN1-Mediated Calcineurin Impairment Drives Sympathetic Outflow in Hypertension.Circulation research · 2025Article
- Calcineurin in cancer signaling networks.Nagoya journal of medical science · 2025Review
- Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1-TFEB pathway to Huntington's disease neurodegeneration.Nature aging · 2024Article
- Funneling modulatory peptide design with generative models: Discovery and characterization of disruptors of calcineurin protein-protein interactions.PLoS computational biology · 2023Article
- A cellular atlas of calcineurin signaling.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells.iScience · 2022Article
- RCAN1-mediated calcineurin inhibition as a target for cancer therapy.Molecular medicine (Cambridge, Mass.) · 2022Review
- Decoding the Phosphatase Code: Regulation of Cell Proliferation by Calcineurin.International journal of molecular sciences · 2022Review
- Integrative genomic analysis of PPP3R1 in Alzheimer's disease: a potential biomarker for predictive, preventive, and personalized medical approach.The EPMA journal · 2021Article
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- A Review of Calcineurin Biophysics with Implications for Cardiac Physiology.International journal of molecular sciences · 2021Review
- Advancements in chemical biology targeting the kinases and phosphatases of RNA polymerase II-mediated transcription.Current opinion in chemical biology · 2021Review
- Interplay of RNA-Binding Proteins and microRNAs in Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- Immune Dysregulation and the Increased Risk of Complications and Mortality Following Respiratory Tract Infections in Adults With Down Syndrome.Frontiers in immunologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Regulator of calcineurin 1 (RCAN1) is an endogenous inhibitor of the Ser/Thr phosphatase calcineurin (CN). It has been shown that excessive inhibition of CN is a critical factor for Down syndrome and Alzheimer's disease. Here, we determined RCAN1's mode of action. Using a combination of structural, biophysical, and biochemical studies, we show that RCAN1 inhibits CN via multiple routes: first, by blocking essential substrate recruitment sites and, second, by blocking the CN active site using two distinct mechanisms. We also show that phosphorylation either inhibits RCAN1-CN assembly or converts RCAN1 into a weak inhibitor, which can be reversed by CN via dephosphorylation. This highlights the interplay between posttranslational modifications in regulating CN activity. Last, this work advances our understanding of how active site inhibition of CN can be achieved in a highly specific manner. Together, these data provide the necessary road map for targeting multiple neurological disorders.
Identifiers
What OpenQuestion holds
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.