Abstract
The C-terminal fragment of CABIN1 interacts with calcineurin and represses the transcriptional activity of the nuclear factor of activated T cells (NFAT). However, the specific sequences and mechanisms through which it binds to calcineurin are unclear. This study determined that decameric peptide (CABIN1 residues 2146-2155) is minimally required for binding to calcineurin. This peptide contains a unique "PPTP" C-terminal sequence and a "PxIxIT" N-terminal motif. Furthermore, p38MAPK phosphorylated the threonine residue of the "PPTP" sequence under physiological conditions, dramatically enhancing the peptide's binding affinity to calcineurin. Therefore, the CABIN1 peptide inhibited the calcineurin-NFAT pathway and the activation of T cells more efficiently than the VIVIT peptide without affecting calcineurin's phosphatase activity. The CABIN1 peptide could thus be a more potent calcineurin inhibitor and provide therapeutic opportunities for various diseases caused by the calcineurin-NFAT pathway.