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| Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life |
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| Author(s): Genesca L, Aubareda A, Fuentes JJ, Estivill X, De la Luna S, Perez-Riba M |
| Source: BIOCHEMICAL JOURNAL Volume: 374 Pages: 567-575 Part: Part 2 Published: SEP 1 2003 |
| Times Cited: 33 References: 40 |
| Abstract: Calcipressin 1 is an endogenous inhibitor of calcineurin, which is a serine/threonine phosphatase under the control of Ca2+ and calmodulin. Calcipressin I 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 I isoform I 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-nnediated transcriptional activation. We demonstrate for the first time that endogenous calcipressin I exists as a complex together with the calcineurin A and B heterodimer. Calcipressin I 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 I 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 I is involved in the regulation of the phosphatase activity of calcineurin and can therefore act as a modulator of calcineurin-dependent cellular pathways. |
| Document Type: Article |
| Language: English |
| Reprint Address: Perez-Riba, M (reprint author), CRG, Genes & Dis Program, Passeig Maritim 37-49, Barcelona 08003, Spain |
Addresses:
1. CRG, Genes & Dis Program, Barcelona 08003, Spain
2. IRO, Med & Mol Genet Ctr, Barcelona 08907, Spain
3. Hosp Llobregat, Barcelona, Spain
4. ICREA, Barcelona, Spain |
| Publisher: PORTLAND PRESS, 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 721LL |
| ISSN: 0264-6021 |
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