Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life

Lali Genescà, Anna Aubareda, Juan J. Fuentes, Xavier P. Estivill, Susana De La Luna, Mercè Pérez-Riba

Research output: Contribution to journalArticle

74 Citations (Scopus)

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 languageEnglish
Pages (from-to)567-575
Number of pages9
JournalBiochemical Journal
Volume374
Issue number2
DOIs
Publication statusPublished - 1 Sep 2003
Externally publishedYes

Fingerprint

Phosphorylation
Calcineurin
Half-Life
Exons
Protein Isoforms
Chromosomes, Human, Pair 21
Peptides
Phosphoprotein Phosphatases
Phosphoproteins
Human Chromosomes
Calmodulin
Transcriptional Activation
Chromosomes
Phosphoric Monoester Hydrolases
Modulators
Amino Acids
Genes
Chemical activation
Degradation

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 journalArticle

Genescà, Lali ; Aubareda, Anna ; Fuentes, Juan J. ; Estivill, Xavier P. ; De La Luna, Susana ; Pérez-Riba, Mercè. / Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life. In: Biochemical Journal. 2003 ; Vol. 374, No. 2. pp. 567-575.
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