【正文】
cytochrome c from IO space of Mit. Form a multisubunit plex。 ced4 同源區(qū)( 320Aa) 。 Adaptor N端的 DED(death effector domain): 誘導(dǎo) caspase8活化。 Apoptosis is carried out by a proteolytic system — caspase (1) Why called caspase? Active site: Cysteine Cleavage site: Asparatic acid Cysteine Asparatic acid specific protease ApsXxx 天冬氨酸特異性的半光氨酸蛋白水解酶 ,負(fù)責(zé)選擇性的切割某些蛋白質(zhì) ,切割的結(jié)果是使其活化或失活 ,非完全降解 .分為兩類 ,一類為凋亡的起始者 ,一類為凋亡的執(zhí)行者 . Caspase依賴性的細(xì)胞凋亡 Apoptosis can be divided into two phases: ?Activation phase: The cell responds to “death signals” that mit it to undergoing selfdestruction. ?Execution phase: The death sentence is carried out. Apoptosis cells are recognized by phagocytes because they carry exposed markers, called “eat me” signals. The best studied “eat me” signal is the presence of phosphatidylserine molecules in the outer leaflet of PM of apoptotic cells (by flopflipase). How to activate caspases? All caspases expressed as proenzymes— Procaspases Procaspase NH2terminal prodomain: Highly variable Large subunit (20kD) Small subunit (10kD) How are procaspases activated to initiate the caspase cascade? The activation is triggered by adaptor proteins that bring multiple copies of specific procaspases. 3 groups of caspase: apoptotic initiators: caspase2, caspase8, caspase9 and caspase10 apoptotic executioners: caspase3, caspase6 , caspase7 and 14 (morphology change) inflammatory mediateors: caspase1, and caspase11 Procaspases are activated by binding to adaptor proteins The caspase cascade involved in apoptosis A. Procaspase activation by proteolytic cleavage. B. Caspase cascade The target proteins of caspase are the following: ?More than a dozen protein kinase, including FAK, PKC, and Raf1. FAK– disrupt cell adhesion for the apoptotic cell. ?Lamins. Cleavage of lamins leads to the disassembly of the nuclear lamina and shrinkage of the nucleus. ?Proteins required for cell structure. Such as IF, actin, and gelsilin. Cleavage and inactivation of these proteins lead to changes in cell shap