(精编)【医学教学课件】细胞增生与凋亡的分子机制.pptVIP

;;;;;Nobel Prize for Physiology and Medicine 2002;Sydney Brenner H. Robert Horvitz John Sulston;;第一节 生长因子信号转导活化细胞周期是细胞增生的分子机制;The 4 phases of a typical cell cycle and the events occurring during each phase are outlined;四、生长因子等通过信号转导调控细胞周期;Apoptosis:;Programmed Cell Death in Eukaryotes;Caenorhabditis elegans:The Perfect Model;Approximately 40 percent of the worm’s genes are also found in humans Responds to taste, smell, temperature, touch, and possibly light So, where did the other 131 cells go?;The C. elegans Organism;The Fundamental Genes Being Examined;EGL-1…has multiple mammalian killer gene counterparts CED-3…human counterparts are called caspases which initiate apoptosis; protein ICE CED-4…human counterpart called Apaf1 which promotes caspase activation CED-9…comparable to the human oncogene BCL-2 which blocks cell suicide;Major Players in Apoptosis---caspase;;Plays an integral role in regulating mitochondrial outer membrane permeabilization, and thus the release of key effector proteins including cyto c and Smac/DIABLO from the mit intermembrane space At least 20 Bcl-2 related proteins identified in mammalian cells Bcl-2 family members share one or more Bcl-2 homology (BH) domains and are divided into two main groups – whether they promote or inhibit apoptosis Anti-apoptotic members such as Bcl-xL, Bcl-w and Boo/Diva share at least three or four regions of extensive amino acid sequence similarity with the prototypical Bcl-2 (BH1 – BH4 regions) Pro-apoptotic members usually posses only a BH3 region – e.g. Bad, Bik/Nbk/Blk, and Bid Bax-Bak – examples of pro-apoptotic multidomain proteins ;Bcl-2 family;Major Players in Apoptosis---adaptor protein;Suppress apoptosis triggered by wide variety of stimuli – e.g. viral infection, chemotherapeutic drugs and components of the TNF-a/Fas signaling pathway Characterized by one or more repeats of highly conserved ~70 amino acid domain termed baculoviral IAP repeat (BIR) Currently six human IAP members – c-