八单元细胞衰老和凋亡教程.ppt

* * * tTG催化细胞内蛋白质交联、聚合，有助于保持凋亡小体的完整性，防止有害物质渗漏 * They won the Nobel Prize in Physiology or Medicine 2002 for their discoveries concerning genetic regulation of organ development and programmed cell death on the C. elegans. * Humans have 15 different caspases, all of which are initially made as procaspases that must be cleaved to become active. * Gelsolin凝溶胶蛋白 keratins角蛋白，拓扑异构酶Topoisomerases 1) Inactivation of enzymes involved in DNA repair. The enzyme poly (ADP-ribose) polymerase, or PARP, was one of the first proteins identified as a substrate for caspases. PARP is involved in repair of DNA damage and functions by catalyzing the synthesis of poly (ADP-ribose) and by binding to DNA strand breaks and modifying nuclear proteins. The ability of PARP to repair DNA damage is prevented following cleavage of PARP by caspase-3. 2) Breakdown of structural nuclear proteins. Lamins are intra-nuclear proteins that maintain the shape of the nucleus and mediate interactions between chromatin and the nuclear membrane. Degradation of lamins by caspase 6 results in the chromatin condensation and nuclear fragmentation commonly observed in apoptotic cells. 3) Fragmentation of DNA. The fragmentation of DNA into nucleosomal units - as seen in DNA laddering assays - is caused by an enzyme known as CAD, or caspase activated DNase. Normally CAD exists as an inactive complex with ICAD (inhibitor of CAD). During apoptosis, ICAD is cleaved by caspases, such as caspase 3, to release CAD. Rapid fragmentation of the nuclear DNA follows * One of the hallmarks of apoptosis is the cleavage of chromatin into nucleosomal units. The caspases play an important role in this process by activating DNases, inhibiting DNA repair enzymes and breaking down structural proteins in the nucleus. * All known apoptosis signalling pathways converge on the caspases, a family of proteases that form a self-amplifying cascade. Caspases are constitutively expressed in cells. However, to prevent them from inadve