A calcium-dependent nuclease from apoptotic rat thymocytes is homologous with cyclophilin. Recombinant cyclophilins A, B, and C have nuclease activity.

Apoptosis is an important physiological process that involves the deletion of specific cells in a controlled and timely manner. A biochemical hallmark typifying apoptosis in normal lymphocytes is DNA cleavage caused by a calcium-dependent nuclease. We have previously identified and purified an 18-kDa nuclease (NUC18) from glucocorticoid-treated rat thymocytes whose activity is associated with this apoptotic DNA fragmentation. Partial protein sequencing of pure NUC18 has generated two peptide sequences that have a remarkable similarity to rat cyclophilin A and other members of the cyclophilin family. We report here that recombinant cyclophilins A, B, and C have a calcium/magnesium-dependent nuclease activity with biochemical and pharmacological properties similar to those of NUC18. Our results raise the intriguing possibility that cyclophilin or a cyclophilin-related protein may play a role in lymphocyte apoptosis.