The CALPORTIN principle

The transcription factor NFAT, responsible for the activation of genes that can induce heart failure, is de-phosphorylated by Calcineurin. Subsequently, NFAT is shuttled into the nucleus. To develop its full transcriptional activity NFAT requires nuclear Calcineurin. The translocation of Calcineurin is carried out by a shuttling protein, the Importin β1. Thus, NFAT activates genes that initiate pathological changes finally leading to heart failure (left panel).

We developed the small peptide CALPORTIN (‘CP’ in the right panel) that blocks the interaction of Importin β1 and Calcineurin. Calcineurin is not translocated into the nucleus and thus NFAT is unable to activate genes, that lead to a weakening of the heart.