第五章 程序性细胞死亡apoptosis.pptVIP

Role of Bcl-2 family: I. Regulating mitochondrion integrity Role of Bcl-2 family: II. Regulating initiator caspases Mechanisms of restraining pro-apoptotic proteins Extrinsic cell death pathway Death receptor-mediated apoptosis 8 Death Receptors containing death domain (DD): TNFR1 (DR1/CD120a/P55/P60) Fas (DR2/CD95/APO-1) DR3 (APO3/LARD/TRAMP/WSL1) TRAILR1 (DR4/APO-2): TNF-related apoptosis-inducing ligand receptor 1 TRAILR2 (DR5/KILLER/TRICK2) DR6 EDAR: ectodysplasin A receptor NGFR: nerve growth factor receptor Two types of DR signaling complexes Type I DR-signaling complex: FAS Type I: Fas, TRAILR1, TRAILR2 formation of DISC (death-inducing signaling complex) to activate caspase-8 or caspase 10 DISC: DR, FADD (Fas-associated death domain protein), procaspase-8 FLIPL and FLIPs inhibit caspase-8 Activation by blocking its processing Two types Fas-signaling: enough caspase-8 (thymocytes) or less caspase-8 to cleave bid for further amplification of death signals through mitochondria (hepatocytes) Fas signaling Type II DR signaling complex Type II: TNFR1, DR3, DR6 and EDAR Recruit different set of molecules to transduce both apoptotic and survival signals formation of two signaling complexes: Complex I: TNF, TNFR1, RIP(receptor interacting protein) TRADD (TNFR-associated death domain protein) TRAF-1/2 (TNFR-associated factor), no FADD and caspase-8, triggers NF-KB pathway Complex II: translocation of complex I to cytosol to recruit FADD, procaspase-8/10 and form traddosome to activate caspase-8/10 Summary Conclusions Programmed cell death is evolutionarily Conserved from C. elegans to humans 2. Two major apoptosis pathways are involved in mammals 3. More mechanisms to uncover………… Papers to read Condrat B and Xue D. Programmed cell death. Wormbook Danial N and Korsmeyer S. Cell death: Critical Control Points Cell 116, 205-219, 2004 2. Cory S and Adams JM, The Bcl2 fami