Orth K, Chinnaiyan A M, Garg M, Froelich C J, Dixit V M
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
J Biol Chem. 1996 Jul 12;271(28):16443-6.
Phylogenetic analysis of the CED-3/ICE family of cysteine proteases suggests the existence of a subfamily most related to the Caenorhabditis elegans death gene ced-3 and includes Yama (CPP32, apopain), LAP3 (Mch3, CMH1), and Mch2. Here, we show that Mch2 is processed from its zymogen form to a proteolytically active dimeric species during execution of the apoptotic program and by the cytotoxic T cell death protease granzyme B. Additionally, like Yama and LAP3, Mch2 functions downstream of the death inhibitors Bcl-2, Bcl-xL, and CrmA. Importantly, Mch2, but not Yama or LAP3, is capable of cleaving lamin A to its signature apoptotic fragment, indicating that Mch2 is an apoptotic laminase.
对半胱氨酸蛋白酶CED-3/ICE家族的系统发育分析表明，存在一个与秀丽隐杆线虫死亡基因ced-3关系最为密切的亚家族，其中包括Yama（CPP32，凋亡蛋白酶）、LAP3（Mch3，CMH1）和Mch2。在此，我们表明，在凋亡程序执行过程中以及通过细胞毒性T细胞死亡蛋白酶颗粒酶B，Mch2从其酶原形式被加工成具有蛋白水解活性的二聚体形式。此外，与Yama和LAP3一样，Mch2在死亡抑制剂Bcl-2、Bcl-xL和CrmA的下游发挥作用。重要的是，Mch2能够将核纤层蛋白A切割成其标志性的凋亡片段，而Yama或LAP3则不能，这表明Mch2是一种凋亡核纤层蛋白酶。
