Montague J W, Gaido M L, Frye C, Cidlowski J A
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599.
J Biol Chem. 1994 Jul 22;269(29):18877-80.
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.
细胞凋亡是一个重要的生理过程，涉及以可控且及时的方式清除特定细胞。正常淋巴细胞中典型的细胞凋亡生化标志是由钙依赖性核酸酶引起的DNA裂解。我们之前从糖皮质激素处理的大鼠胸腺细胞中鉴定并纯化了一种18 kDa核酸酶（NUC18），其活性与这种凋亡性DNA片段化有关。对纯NUC18进行的部分蛋白质测序产生了两个与大鼠亲环素A及亲环素家族其他成员具有显著相似性的肽序列。我们在此报告，重组亲环素A、B和C具有钙/镁依赖性核酸酶活性，其生化和药理学特性与NUC18相似。我们的结果提出了一个有趣的可能性，即亲环素或亲环素相关蛋白可能在淋巴细胞凋亡中起作用。
