信号转导2－生化课05幻灯片.ppt

To be, or not to be, that is a question! Apoptosis is a tightly regulated process. 1. The shift of balance between death survival signals determined the cell fate (命运） 2. Usually required a number of events (or genes) to control apoptosis E.g., activation of one oncogenes induce apoptosis in most cases, inhibit apoptosis only with the support from other signals. (Together we stand, separate we died) 双向调控基因 — c-Myc的作用模型 肿瘤形成必须是在单个细胞中发生多重遗传突变 单个癌基因激活和抑癌基因失活不足以引起肿瘤细胞的显著扩增， 因为细胞对凋亡的易感性也同时增加；凋亡抑制是肿瘤细胞能够生长到足以威胁宿主所必须的；例如： Rb的失活仅会促进p53依赖的凋亡，但不会引起肿瘤，除非细胞的凋亡过程被抑制； Apoptosis and oncogenesis 细胞信号转导调控与疾病防治 Regulation of cellular signal  transduction in prevention  and treatment of diseases 以信号转导蛋白为靶分子对疾病进行防治 STI571 as a paradigm (范例）for cancer therapy In 1960, described the presence of a consistent chromosomal abnormality in CML（一种白血病)，so-called Philadelphia chromosome (Ph) A reciprocal translocation between the long arms of chromosomes 9 and 22, t(9:22)(q34;q11), The molecular consequence of this event is the generation of a chimeric bcr-abl gene (22:9) The tyrosine kinase activity of Bcr-Abl stimulates a variety of signaling pathways, leading to alterations in survival properties of cells STI571 an Abl-specific tyrosine kinase inhibitor Before the discovery of this drug, most CML patients died within 6 month 具备勇气和智慧 * 细胞到达感染部位，就会碰到病原。病原进入细胞有侵袭或吞噬两种方式 我们研究这两种方式对凋亡的影响及机制 发现病原侵袭可通过直接激活Rac和Cdc42等死亡信号来诱导细胞凋亡并损坏粘膜屏障 。 调理引起的吞噬虽然也激活死亡信号Rac和Cdc42，但对凋亡无影响。 进一步研究发现，吞噬过程通过活化酪氨酸激酶及PI-3K等同时产生生存信号Akt，来拮抗死亡信号的作用，而使细胞免于凋亡。这些结果表明：凋亡是由细胞内“死亡”与“生存”信号之间的精密平衡来决定的，而不是单纯由病原引起，任何干扰该平衡的因素均可改变病原对细胞凋亡的最终影响。1.10” * * Mechanisms by which hormones, retinoids, and Vit. D regulate gene expression Hormone (H), carried to the target tissue on serum binding prot, diffuses across the PM and binds to its specific receptor protein (Rec) in the nucleus. H binding changes the conformation of Rec; forms homo or heterodimers and binds to specific R regions called hormone response elements