Mouse Rcan1 Knockout Project (CRISPR/Cas9)
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The RCAN Carboxyl End Mediates Calcineurin Docking-Dependent Inhibition Via a Site That Dictates Binding to Substrates and Regulators
The RCAN carboxyl end mediates calcineurin docking-dependent inhibition via a site that dictates binding to substrates and regulators Sara Martı´nez-Martı´neza,1, Lali Genesca` b,1,2, Antonio Rodrı´gueza,c, Alicia Rayab, Eula`lia Salichsb, Felipe Werea, Marı´aDolores Lo´pez-Maderueloa, Juan Miguel Redondoa,3, and Susana de la Lunab,d,4 aDepartment of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; bGenes and Disease Program, Centre de Regulacio´Geno`mica, Universitat Pompeu Fabra and CIBER de Enfermedades Raras, 08003 Barcelona, Spain; cDepartamento de Biología Molecular, Facultad de Ciencias, Universidad Auto´noma de Madrid, 28049 Madrid, Spain; and dInstitucio´Catalana de Recerca i Estudis Avanc¸ats, 08010 Barcelona, Spain Edited by Tony Pawson, Mt. Sinai Hospital, Toronto, ON, Canada, and approved February 25, 2009 (received for review December 12, 2008) Specificity of signaling kinases and phosphatases toward their CN activity is also regulated by interaction with anchoring and targets is usually mediated by docking interactions with substrates regulatory proteins (11); however, little is known about how these and regulatory proteins. Here, we characterize the motifs involved proteins form contacts with CN. Among the regulatory proteins, in the physical and functional interaction of the phosphatase one of the most remarkable families is the recently renamed calcineurin with a group of modulators, the RCAN protein family. regulator of calcineurin (RCAN, previously known as DSCR/ Mutation of key residues within the hydrophobic docking-cleft of MCIP/calcipressin/Adapt78 in mammals) (12). RCANs bind to and the calcineurin catalytic domain impairs binding to all human RCAN inhibit CN-mediated activities in vitro (13–18). -
Protein Kinase CK2-Dependent Phosphorylation of the Human Regulators of Calcineurin Reveals a Novel Mechanism Regulating the Calcineurin–Nfatc Signaling Pathway
CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1833 (2013) 2311–2321 Contents lists available at SciVerse ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamcr Protein kinase CK2-dependent phosphorylation of the human Regulators of Calcineurin reveals a novel mechanism regulating the calcineurin–NFATc signaling pathway Sergio Martínez-Høyer a, Álvaro Aranguren-Ibáñez a, Javier García-García b, Eva Serrano-Candelas a, Jordi Vilardell c, Virginia Nunes e, Fernando Aguado d, Baldo Oliva b, Emilio Itarte c, Mercè Pérez-Riba a,⁎ a Cellular Signaling group, Cancer and Molecular Genetics Program, Bellvitge Biomedical Research Institute — IDIBELL, L'Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain b Structural Bioinformatics Goup (GRIB-IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona Research Park of Biomedicine (PRBB), 08003 Barcelona, Catalonia, Spain c Unitat de Bioquímica de Biociències, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia, Spain d Department of Cell Biology, University of Barcelona, Barcelona, Spain e Laboratorio de Genética Molecular, IDIBELL, 2U-730 (CIBERER), and Departament de Ciències Fisiològiques II, Facultad de Medicina, Universitat de Barcelona, Barcelona, Spain article info abstract Article history: Cyclosporine A and FK506 produce immunosuppression by blocking calcineurin phosphatase activity and Received 14 December 2012 consequently activation of cytosolic Nuclear Factor of Activated T-cell (NFATc) transcription factor. Due to Received in revised form 21 May 2013 the chronic toxicity associated with their administration, the development of more specific immunosuppres- Accepted 22 May 2013 sants is currently an important unmet medical need. -
The RCAN Carboxyl End Mediates Calcineurin Docking-Dependent Inhibition Via a Site That Dictates Binding to Substrates and Regulators
The RCAN carboxyl end mediates calcineurin docking-dependent inhibition via a site that dictates binding to substrates and regulators Sara Martı´nez-Martı´neza,1, Lali Genesca` b,1,2, Antonio Rodrı´gueza,c, Alicia Rayab, Eula` lia Salichsb, Felipe Werea, Marı´a Dolores Lo´ pez-Maderueloa, Juan Miguel Redondoa,3, and Susana de la Lunab,d,4 aDepartment of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; bGenes and Disease Program, Centre de Regulacio´ Geno` mica, Universitat Pompeu Fabra and CIBER de Enfermedades Raras, 08003 Barcelona, Spain; cDepartamento de Biología Molecular, Facultad de Ciencias, Universidad Auto´ noma de Madrid, 28049 Madrid, Spain; and dInstitucio´ Catalana de Recerca i Estudis Avanc¸ats, 08010 Barcelona, Spain Edited by Tony Pawson, Mt. Sinai Hospital, Toronto, ON, Canada, and approved February 25, 2009 (received for review December 12, 2008) Specificity of signaling kinases and phosphatases toward their CN activity is also regulated by interaction with anchoring and targets is usually mediated by docking interactions with substrates regulatory proteins (11); however, little is known about how these and regulatory proteins. Here, we characterize the motifs involved proteins form contacts with CN. Among the regulatory proteins, in the physical and functional interaction of the phosphatase one of the most remarkable families is the recently renamed calcineurin with a group of modulators, the RCAN protein family. regulator of calcineurin (RCAN, previously known as DSCR/ Mutation of key residues within the hydrophobic docking-cleft of MCIP/calcipressin/Adapt78 in mammals) (12). RCANs bind to and the calcineurin catalytic domain impairs binding to all human RCAN inhibit CN-mediated activities in vitro (13–18). -
2Nd ECS Workshop 2009 Annexins, Targets and Calcium-Binding Proteins in Pathology Smolenice, June 3–6, 2009, Slovakia
F1 Focus Issue 2nd ECS Workshop 2009 Annexins, targets and calcium-binding proteins in pathology Smolenice, June 3–6, 2009, Slovakia Editors A. Breier, C. W. Heizmann and B. Uhrík F2 Gen. Physiol. Biophys. (2009), 28, Focus Issue, F2 Preface The 2nd ECS Workshop on Annexins, Targets and Calcium-Binding Proteins in Pathology This workshop was held in the beautiful Smolenice castle in Slovakia from June 3-6, 2009 and organized by the European Calcium Society (Claus Heizmann) in cooperation with the Slovak Academy of Sciences (Albert Breier). The village of Smolenice is located in the west of Slovakia, about 60 km from the capital city of Bratislava. The Smolenice castle is located above the village on the foothills of the Carpatian mountains. First documents of the existence of this castle date back to the 13th century. During the Napoleon war the castle de- cayed after the main building and the tower had been destroyed. Reconstruction of the castle was started early in the 20th century. In 1953 the castle was handed over to the Slovak Academy of Sciences (SAS) to become their representative International Congress Center. 65 scientists (mostly young investigators) attended this 2nd ECS workshop; the participants came from 15 different countries including Argentina, Canada, USA, Russia and Poland. The scientific program opened with the keynote lecture of Joseph Metzger (University of Minnesota, Minneapolis) dis- cussing the defective intracellular calcium handling in diastolic heart failure (DHF) and the gene transfer of parvalbumin restoring myocardial performance in DHF. The next day two sessions followed discussing the structures and functions of annexins and their interactions with target proteins with the emphasis on the EF-hand calcium-binding proteins sorcin and S100 proteins. -
The Regulator of Calcineurin (RCAN1) an Important Factor Involved in Atherosclerosis and Cardiovascular Diseases Development
Journal of Medicine and Life Vol. 7, Issue 4, October-December 2014, pp.481-487 The regulator of calcineurin (RCAN1) an important factor involved in atherosclerosis and cardiovascular diseases development Torac E, Gaman L, Atanasiu V Biochemistry Department, ”Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Correspondence to: Elena Torac, PhD student Biochemistry Department, ”Carol Davila” University of Medicine and Pharmacy, 8 Eroilor Sanitari Blvd., District 5, 050474, Bucharest Mobile phone: 0723330110, E-mail: [email protected] Received: June 14th, 2014 – Accepted: September 20th, 2014 Abstract Atherosclerosis, one of the main causes of cardiovascular diseases, is a complex process that involves manifold factors. Besides the vascular lipids accumulation, inflammatory factors could be considered as a proatherogenic factor – RCAN1. RCAN1 is a regulator of calcineurin, both of them being calcium dependent proteins. Recent studies have shown that RCAN1 has an important role in heart valve development. In the same time researchers found that, the atherosclerotic plaques have an up-regulated RCAN1 gene expression. In the near future, it is desirable to elucidate the RCAN1 function and classify it as a possible biochemical marker to diagnose infancy atherosclerosis. Keywords: RCAN1, atherosclerosis, calcineurin, cardiovascular disease, Down Syndrome Abbreviations: RCAN1 = regulator of calcineurin, LDL = low density lipoproteins, HMG-CoA – 3 = hydroxy-3-methylglutaryl coenzyme A, VSMCs = vascular smooth muscle cells,