肿瘤分子生物学4.细胞周期分子调控与细胞凋亡.ppt

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * The fate of Apoptotic Cells benefit to neighboring cells Phagocytic recognition of an apoptotic cell. At present, little is known about the interactions between apoptotic cells and phagocytes, but a series of molecules seem to be important including phosphatidylserine (PS), anionic phospholipids, and intracellular adhesion molecule 3 (ICAM 3). The hierarchical nature of these interactions is not yet known but recent evidence suggests that ICAM 3 partners CD14 on the macrophage. An important pairing also seems to be between PS and the vitronectin receptor or CD36. This probably occurs via thrombospondin, which can avidly bind both molecules on the phagocyte. Anionic phospholipids Phosphatidyl serine (PS) Vitronectin receptor Thrombospondin May bridge with PS Phagocyte Apoptotic cell * Death Domain-细胞凋亡 Fas–associated protein with death domain TNF receptor-1–associated death domain protein Apoptosis * Fas-Proliferation/Apoptosis （I） * Death Receptor Signalling * DNA损伤-p53-细胞的命运 Classical Contemporary Views of DNA Damage Response *: mutation * 细胞凋亡的发生机制 * Interlocking Relations between Oncoproteins Ras, Myc and Bcl-2 * Nucleus and Mitochondria are the depository of genes * Mitochondrial Control of Apoptosis * Inhibition of Apoptosis (a) The normal cell cycle. (b) Apoptosis in the cell cycle Anat.Histol.Embryol. 31, 214–223 (2002) Apoptosis in Cell Cycle (G1/S) * Schematic representation of apoptotic events Toxicol Pathol.?2007;?35(4): 495–516 * Multiple Pathways of Apoptosis * The PERK pathway 细胞坏死(necrosis) 通常由严重损伤因素(如毒物中毒、严重缺血、缺氧、强酸、强碱、强大电流、高温等)所致 细胞凋亡（apoptosis） 细胞在激素、生长因子、理化因素、免疫因素、微生物学因素等作用下，由死亡基因调控各种死亡信号转导通路，激活上游的起始caspases和下游的效应caspases以及相关酶类，使细胞发生特征性的生化和形态学改变。 细胞凋亡和细胞坏死的诱发因素 * 细胞凋亡与肿瘤临床治疗 放疗 Tumor cell 早期应答基因活化 Apoptosis 化疗 Tumor cell