细胞凋亡的信号转导通路.ppt

细胞凋亡的信号转导通路 死亡受体信号通路 线粒体信号通路 内质网和高尔基体的信号通路 细胞凋亡的基因调控 * Apoptosis - (Gr. falling) a process seen in multicellular organisms, by which specific cells are killed and removed for the benefit of the organism. Kerr, J.F.R., Wyllie, A.H. and Currie, A.R. 1972. Br. J. Cancer 26:239. Apoptosis----------Death Receptor Signaling TNF receptor superfamily Apoptosis Cell death Fas FasL TNF-R1 TNF TRADD FADD Cas8 Caseff Mit Cyt c Protein degradation DNase Caspase活化的三种方式 Caspase的活化 Caspase-independent signaling pathways  Mitochondrial Control of Apoptosis 内质网内钙离子稳态的改变可作用于内质网功能的多个环节，引发细胞凋亡。内质网钙离子的释放在多种凋亡实验中被观察到。内质网的钙释放参与Bad和caspase在不同诱因凋亡中的激活。 破坏内质网内钙离子的稳态可以导致内质网应激，包括内质网超负荷反应，激活凋亡通路。其中内质网超负荷反应以激活转录因子NF-kB为主要特点，启动多种前炎性蛋白和细胞粘附分子的转录表达，对凋亡进行调控。 内质网信号通路 Science. 2007 Nov 9;318(5852):944-9. 过度内质网应激也可能涉及线粒体及细胞色素C的协同作用而使caspase激活和细胞凋亡。内质网应激介导细胞凋亡调节的一个主要因素是Caspase-12。 在多种疾病的发生发展中，内质网在完成基本生理功能的同时，作为信号传导的枢纽平台，对于细胞凋亡过程发挥着重要的调控作用。 * * * The CD95 system The growing subfamily of death receptors is part of the TNF/NGF-receptor superfamily. This superfamily is characterized by a sequence of 2 to 5 cysteine-rich extracellular repeats. The death receptors contain an intracellular death domain (DD), which is essential for transduction of the apoptotic signal. Six members of this subfamily are known so far, namely TNF-R1 (CD120a), CD95 (APO-1/Fas), DR3 (APO-3, LARD, TRAMP, WSL1), TRAIL-R1 (APO-2, DR4), TRAIL-R2 (DR5, KILLER, TRICK2), and DR6.? Death receptors are activated by their natural ligands which have co-evolved as a death ligand family, called the TNF family. Except for LTa, the death ligands are type II transmembrane proteins, which can be converted into a soluble form by the activity of metalloproteases. Several groups reported activity of the soluble CD95L, whereas others ascribe the capacity to induce apoptosis to the membrane bound form. Recently, it has been proposed that the activity of soluble CD95L is enhanced by interaction with the