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.
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599.
J W
JW
Montague
M L
ML
Gaido
C
C
Frye
J A
JA
Cidlowski
D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology; D019696:Peptidylprolyl Isomerase; D051381:Rats; D011994:Recombinant Proteins; D013379:Substrate Specificity; D013950:Thymus Gland / Q000166:cytology*; D015032:Zinc / Q000494:pharmacology
D002352:Carrier Proteins; D011994:Recombinant Proteins; D001312:Aurintricarboxylic Acid; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; C071211:endonuclease NUC18; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D015032:Zinc