Abstract
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.
Original language | English |
---|---|
Pages (from-to) | 567-575 |
Number of pages | 9 |
Journal | Biochemical Journal |
Volume | 374 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Sep 2003 |
Externally published | Yes |
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Keywords
- Calcineurin endogenous inhibitor
- Calcipressin
- DSCR1
- FLISPP motif
- NF-AT
- PP-2B
ASJC Scopus subject areas
- Biochemistry
Cite this
Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life. / Genescà, Lali; Aubareda, Anna; Fuentes, Juan J.; Estivill, Xavier P.; De La Luna, Susana; Pérez-Riba, Mercè.
In: Biochemical Journal, Vol. 374, No. 2, 01.09.2003, p. 567-575.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life
AU - Genescà, Lali
AU - Aubareda, Anna
AU - Fuentes, Juan J.
AU - Estivill, Xavier P.
AU - De La Luna, Susana
AU - Pérez-Riba, Mercè
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
KW - Calcineurin endogenous inhibitor
KW - Calcipressin
KW - DSCR1
KW - FLISPP motif
KW - NF-AT
KW - PP-2B
UR - http://www.scopus.com/inward/record.url?scp=0041761256&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041761256&partnerID=8YFLogxK
U2 - 10.1042/BJ20030267
DO - 10.1042/BJ20030267
M3 - Article
C2 - 12809556
AN - SCOPUS:0041761256
VL - 374
SP - 567
EP - 575
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 2
ER -