医学课件 细胞增生和凋亡的分子机制.pptVIP

Other molecules of Apoptosis Omi: most recently discovered proapoptotic protein released from mitochondria and shows much similarity to Smac. Cell death process three phases Induction or initiation phase （起始） Effector or decision phase（效应） activating hydrolase (protease and nuclease) Degradation phase（降解） digestion of protein, fragmentation of DNA Two main apoptotic pathways The activation of death receptors （死亡受体途径） Mitochondria pathway （线粒体途径） common pathway: activation of caspase cascade Major Apoptotic Pathways in Mammalian Cells Hengartner, M.O. 2000. Nature. 407:770. Green, D. and Kroemer, G. 1998. Trends Cell Biol. 8:267. Mitochondrial Pathway Death Receptor Pathway FasL Caspase 3 D D D D Fas/Apo1 /CD95 FADD Procaspase 8 DISC Caspase 8 BID oxidants ceramide others Bcl-2 D Cytochrome c dATP Procaspase 9 Apaf -1 dATP Apaf -1 Caspase 9 Procaspase 3 apoptosome DNA damage Cellular targets Apoptosis Oxygen Society Education Program Tome Briehl 3 DISC: death inducing signal complex FADD: Fas associated protein with death domain 外源性的死亡受体途径 Fas：单跨膜受体，N端在胞外，DD位于胞内，分布广泛 FasL:单跨膜受体，在细胞表面形成三聚体，细胞毒T细胞表面 FADD：Fas-associated death domain DD and DED (death effector domain) DISC：FasL—Fas—FADD Fas and Related Proteins with Death Domains Death receptor: Fas, TNFR1, TNFR2, DR3, DR4, DR5, DcR1,DcR2 TRADD: TNF receptor-associated death domain The extrinsic or death receptor pathway Initiated by binding of a death-inducing ligand to a Cys-rich repeat region in the extracellular domain of a death receptor Death receptors such as Fas and the TNF receptor are integral membrane proteins with their receptor domains exposed at the surface of the cell Binding of the complementary death activator (FasL and TNF-a, respectively) transmits a signal (via an adaptor protein) to the cytoplasm that leads to activation of caspase-8 Caspase-8 (like caspase-9) initiates a cascade of caspase act