半胱氨酸-天冬氨酸蛋白酶(Caspase)及其在细胞凋亡中的作用

Caspase and its effects on apoptosis

白细胞介素β转化酶,即ICE,与线虫死亡基因产物Ced-3蛋白相似,目前已发现14种ICE类似物,Alnemri将ICE家族统一命名为Caspase(Cystein-asparate protease,半胱氨酸-天冬氨酸蛋白酶),Caspase以结构酶原形式广泛存在于细胞。Caspase酶原主要经细胞色素C及死亡受体激活。Caspase活性中心含半胱氨酸,其选择性裂解底物天冬氨酸后残基,通过对蛋白激酶、核酸酶及细胞骨架的裂解,Caspase可激活特定信号系统,产生核皱缩,DNA片段形成等凋亡现象,最终导致细胞死亡,Caspase特异性抑制剂可抑制此作用。许多基因与Caspase参与的凋亡有关。

ICE (interleukin - 1 β- converting enzyme) was found to be similar to the Caenorhabditis elegans cell death gene product CED - 3 in 1993 . Since then, much more attention was paid to ICE family members, and their relationship with apoptosis. At present at least 14 ICE family members have been published. Alnemri gave the family a uniform nomenclature: caspase, caspase - 1 through - 14. Caspase contain a conserved QACXG sequence surrounding the active site eysteine residue. They are constitutively and ubiquitously expressed as catalytically inactive proenzyme composed of a prodomain, a large subunit, and a small unit. Caspase can be activated either by cytochrome C released form mitocondria, or by death -ligand and death - receptor interaction. Besides, RGD can active caspase directly. Forced expression of caspase can induce apoptosis, which can be inhibited by caspase inhibitors. During the induction of apoptosis, caspase is cleaved and activated. After activation caspase can cleave and active several protein kinase, and deoxyribonuclease. They also cleave cytoskeletal protein. These results in cytoplasmic condensation, chromatin condensation, oligonucleosmal DNA fragmentation, and apop-totic body formation. In die end cell will death. Several oncogenes participate in caspase related apoptosis.