Unraveling the molecular mechanisms involved in RCAN-peptide mediated inhibition of calcineurin-NFAT signaling and its potential as an inhibitor of tumor progressions
The calcineurin-NFATc signaling pathway is involved in many aspects of the development and function of the immune, neural, skeletal, cardiovascular and muscular system of vertebrates. Regulators of Calcineurin (RCAN) proteins constitute a family of endogenous regulators of calcineurin, which play an...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2012 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/123913 |
| Acceso en línea: | http://hdl.handle.net/10803/123913 |
| Access Level: | acceso abierto |
| Palabra clave: | Calcineurin NFATc Angiogenesis Immunosupression Mechanism of signal transduction Regulator of Calcineurin (RCAN) Calcineurina CK2 Angiogénesis Inmunosupresión Mecanismos de transducción de señales 577 |
| Sumario: | The calcineurin-NFATc signaling pathway is involved in many aspects of the development and function of the immune, neural, skeletal, cardiovascular and muscular system of vertebrates. Regulators of Calcineurin (RCAN) proteins constitute a family of endogenous regulators of calcineurin, which play an important role in the modulation of the calcineurin-NFATc pathway. Here, we identifiy a novel protein kinase CK2 dependent mechanism by which the CIC motif of RCAN proteins modulate the final signaling output of the pathway. Moreover, we show that the functional CIC motif of RCANs responsible for Cn-NFATc regulation is sufficient to inhibit tumor progression producing a strong anti-angiogenic phenotype in an orthotopic human breast cancer mouse model. Therefore, a CIC-derived peptide has potent immunosuppressive and antitumoral activities by itself. Finally, the results here presented provide important insights for the rational design of potent and specific NFATc inhibitory drugs, which could be of use in autoimmune diseases and cancer. |
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