Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Ignacio Guerrero-Ros
  • Rut ValdorEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101514


Historical Background

The protein family of the regulators of calcineurin (RCANs), previously termed as DSCR, MCIP, or calcipressins among other names, has been shown to function as regulators of the calcium-calmodulin regulated phosphatase calcineurin. The gene encoding for the first RCAN protein was cloned more than 20 years ago and named DSCR1, as it was identified in the Down syndrome critical region, which encoded a proline-rich protein highly...

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  1. Baek KH, Zaslavsky A, Lynch RC, Britt C, Okada Y, Siarey RJ, Lensch MW, Park IH, Yoon SS, Minami T, Korenberg JR, Folkman J, Daley GQ, Aird WC, Galdzicki Z, Ryeom S. Down’s syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature. 2009;459:1126–30.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Cao X, Kambe F, Miyazaki T, Sarkar D, Ohmori S, Seo H. Novel human ZAKI-4 isoforms: hormonal and tissue-specific regulation and function as calcineurin inhibitors. Biochem J. 2002;367:459–66.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Davies KJ, Ermak G, Rothermel BA, Pritchard M, Heitman J, Ahnn J, Henrique-Silva F, Crawford D, Canaider S, Strippoli P, Carinci P, Min KT, Fox DS, Cunningham KW, Bassel-Duby R, Olson EN, Zhang Z, Williams RS, Gerber HP, Perez-Riba M, Seo H, Cao X, Klee CB, Redondo JM, Maltais LJ, Bruford EA, Povey S, Molkentin JD, McKeon FD, Duh EJ, Crabtree GR, Cyert MS, de la Luna S, Estivill X. Renaming the DSCR1/Adapt78 gene family as RCAN: regulators of calcineurin. FASEB J. 2007;21:3023–8.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Ermak G, Hench KJ, Chang KT, Sachdev S, Davies KJ. Regulator of calcineurin (RCAN1-1 L) is deficient in Huntington disease and protective against mutant huntingtin toxicity in vitro. J Biol Chem. 2009;284(18):11845–53.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ermak G, Pritchard MA, Dronjak S, Niu B, Davies KJ. Do RCAN1 proteins link chronic stress with neurodegeneration? FASEB J. 2011;25:3306–11.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Facchin F, Vitale L, Bianconi E, Piva F, Frabetti F, Strippoli P, Casadei R, Pelleri MC, Piovesan A, Canaider S. Complexity of bidirectional transcription and alternative splicing at human RCAN3 locus. PLoS One. 2011;6:e24508.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Fuentes JJ, Pritchard MA, Planas AM, Bosch A, Ferrer I, Estivill X. A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart. Hum Mol Genet. 1995;4:1935–44.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Fuentes JJ, Genesca L, Kingsbury TJ, Cunningham KW, Perez-Riba M, Estivill X, de la Luna S. DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways. Hum Mol Genet. 2000;9:1681–90.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Genesca L, Aubareda A, Fuentes JJ, Estivill X, De La Luna S, Perez-Riba M. Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life. Biochem J. 2003;374:567–75.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Kingsbury TJ, Cunningham KW. A conserved family of calcineurin regulators. Genes Dev. 2000;14:1595–604.PubMedPubMedCentralGoogle Scholar
  11. Liu H, Wang P, Weihong S, Sun X. Degradation of regulator of calcineurin 1(RCAN1) is mediated by both chaperone mediated autophagy and ubiquitin proteosome pathways. FASEB J. 2009;23(10):3383–92.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Martinez-Hoyer S, Sole-Sanchez S, Aguado F, Martinez-Martinez S, Serrano-Candelas E, Hernandez JL, Iglesias M, Redondo JM, Casanovas O, Messeguer R, Perez-Riba M. A novel role for an RCAN3-derived peptide as a tumor suppressor in breast cancer. Carcinogenesis. 2015;36:792–9.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Minami T. Calcineurin-NFAT activation and DSCR-1 auto-inhibitory loop: how is homoeostasis regulated? J Biochem. 2014;155:217–26.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Miyazaki T, Kanou Y, Murata Y, Ohmori S, Niwa T, Maeda K, Yamamura H, Seo H. Molecular cloning of a novel thyroid hormone-responsive gene, ZAKI-4, in human skin fibroblasts. J Biol Chem. 1996;271:14567–71.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Mulero MC, Aubareda A, Schluter A, Perez-Riba M. RCAN3, a novel calcineurin inhibitor that down-regulates NFAT-dependent cytokine gene expression. Biochim Biophys Acta. 2007;1773:330–41.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Ryeom S, Baek KH, Rioth MJ, Lynch RC, Zaslavsky A, Birsner A, Yoon SS, McKeon F. Targeted deletion of the calcineurin inhibitor DSCR1 suppresses tumor growth. Cancer Cell. 2008;13(5):420–31.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Serrano-Candelas E, Farre D, Aranguren-Ibanez A, Martinez-Hoyer S, Perez-Riba M. The vertebrate RCAN gene family: novel insights into evolution, structure and regulation. PLoS One. 2014;9:e85539.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Serrano-Candelas E, Aleman MG, Sole-Sanchez S, Aubareda A, Martinez-Hoyer S, Adan J, Aranguren-Ibanez A, Pritchard MA, Soldevila G, Perez-Riba M. RCAN1 and 3 proteins regulate thymic positive selection. Biochem Biophys Res Commun. 2015;460(2):295–301.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Valdor R, Mocholi E, Botbol Y, Guerrero-Ros I, Chandra D, Koga H, Gravekamp C, Cuervo AM, Macian F. Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation. Nat Immunol. 2014;15:1046–54.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PathologyAlbert Einstein College of MedicineBronxUSA
  2. 2.Department of Human Anatomy and PsychobiologyUniversity of Murcia School of Medicine and Instituto Murciano de Investigación BiosanitariaMurciaSpain