Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life (original) (raw)
Research Article| September 01 2003
∗Genes and Disease Program, Centre de Regulació Genòmica-CRG, Passeig Marítim 37-49, 08003-Barcelona, Spain
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†Medical and Molecular Genetics Centre, Institut de Recerca Oncològica-IRO, Gran Via s/n Km 2.7, 08907-Hospitalet de Llobregat, Barcelona, Spain
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†Medical and Molecular Genetics Centre, Institut de Recerca Oncològica-IRO, Gran Via s/n Km 2.7, 08907-Hospitalet de Llobregat, Barcelona, Spain
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∗Genes and Disease Program, Centre de Regulació Genòmica-CRG, Passeig Marítim 37-49, 08003-Barcelona, Spain
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∗Genes and Disease Program, Centre de Regulació Genòmica-CRG, Passeig Marítim 37-49, 08003-Barcelona, Spain
‡Institució Catalana de Recerca i Estudis Avançats-ICREA, Barcelona, Spain
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†Medical and Molecular Genetics Centre, Institut de Recerca Oncològica-IRO, Gran Via s/n Km 2.7, 08907-Hospitalet de Llobregat, Barcelona, Spain
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Publisher: Portland Press Ltd
Received: February 18 2003
Revision Received: May 30 2003
Accepted: June 17 2003
Accepted Manuscript online: June 17 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 374 (2): 567–575.
Received:
February 18 2003
Revision Received:
May 30 2003
Accepted Manuscript online:
June 17 2003
Calcipressin 1 is an endogenous inhibitor of calcineurin, which is a serine/threonine phosphatase under the control of Ca2+ and calmodulin. Calcipressin 1 is encoded by DSCR1, a gene on human chromosome 21 with seven exons, exons 1–4 are alternative first exons (isoforms 1–4). We show that calcipressin 1 isoform 1 has an N-terminal coding region longer than that previously described, and this generates a new polypeptide of 252 amino acids. This polypeptide is able to interact with calcineurin A and to inhibit NF-AT-mediated transcriptional activation. We demonstrate for the first time that endogenous calcipressin 1 exists as a complex together with the calcineurin A and B heterodimer. Calcipressin 1 is a phosphoprotein that increases its capacity to inhibit calcineurin when phosphorylated at the FLISPP motif, and this phosphorylation also controls the half-life of calcipressin 1 by accelerating its degradation. Additionally, we have also detected further phosphorylation sites outside the FLISPP motif and these contribute to the complex phosphorylation pattern of calcipressin 1. Taking all these results into consideration we suggest that phosphorylation of calcipressin 1 is involved in the regulation of the phosphatase activity of calcineurin and can therefore act as a modulator of calcineurin-dependent cellular pathways.
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The Biochemical Society, London ©2003
2003
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