北京大学：《分子细胞生物学》课程教学资源（PPT课件讲稿，英文版）Chapter 13 Cell apoptosis

Chapter 13 Cell apoptosis 1. Extracellular cotrol of cell division cell growth, and apoptosis I Mitogens stimulate G1-Cdk and g1/s-Cdk activities

Chapter 13 Cell apoptosis 1. Extracellular cotrol of cell division, cell growth, and apoptosis Mitogens stimulate G1-Cdk and G1/S-Cdk activities

090÷13=959(c8ll PRIZED Horvitz, and Sulston share Physiology or Medicine Nobel (2002) for their discoveries concerning genetic regulation of organ development and programmed cell death

PRIZED Horvitz, and Sulston share Physiology or Medicine Nobel （2002） “for their discoveries concerning genetic regulation of organ development and programmed cell death” 1090 –131= 959(cells)

衰老 机体结构← 细胞增殖 细胞分化 细胞凋亡 细胞信号转导 染色体 (DNA与蛋白质的相互作用)

机体结构 细胞增殖 细胞分化 细胞凋亡 细胞信号转导 染色体 （DNA与蛋白质的相互作用） 衰老

X A Simplified model of (MAP kinas one way that mitogens stimulate cell division CYTOSOL NUCLEUS SCF subunit ouno ncrcgsod increased increased p27 degradation E2F synthesis G Cak activ G./s-cdk act cyclin D-C cyclin E-Cok increased phosphorylation E2F activity ENTHY IN S PHASE

A simplified model of one way that mitogens stimulate cell division

Human cells have a built-in limitation on the number of times they can divide The cell division is cotrolled not only by extracellular mitogens but also by intracellular mechanisms that can limit cell proliferation Cell-cycle arrest excessive Myc production or apoptosis induced by ARF p excessive Mdm2 stimulation of mitogenic stable active p53 pathways 53 DEGRADATION cell-cycle OR apoptosis arrest

Human cells have a built-in limitation on the number of times they can divide The cell division is cotrolled not only by extracellular mitogens but also by intracellular mechanisms that can limit cell proliferation. Cell-cycle arrest or apoptosis induced by excessive stimulation of mitogenic pathways

growth factor th factor Extracellular growth factors receptor stimulate cell growth Activation of cell-surface receptors Pl 3-kinas protein kinase activation Activation of pi 3-kinase active active phosphorylated S6 kinase Activation of elF4E (translation increased mRNA translation initiation factor)and s6 kinase(phosphorylates ribosomal STIMULATION OF CELL GROWTH protein S6) Figure 17-44 One way in which growth factors promote cell growt In this simplified scheme, activation of cell-surface receptors leads to the activation of Pl 3-kinase, which promotes Increasing protein synthesis and cell protein synthesis, at least partly through the activation of elF4E and S6 kinase growth Growth factors also inhibit protein breakdown(not shown) by poorly understood pathway

Extracellular growth factors stimulate cell growth Activation of cell-surface receptors Activation of PI 3-kinase Activation of elF4E (translation initiation factor) and S6 kinase(phosphorylates ribosomal protein S6) Increasing protein synthesis and cell growth

2.Apoptosis, Programmed cell death Biological functions of apoptosis X细胞凋亡是多细胞生物在发育过程中,一种由基因控制 的主动的细胞生理性自杀行为 X In development, homeostasis tumor surveillance and the function of the immune system

2.Apoptosis, Programmed cell death Biological functions of apoptosis  In development, homeostasis, tumor surveillance, and the function of the immune system. 细胞凋亡是多细胞生物在发育过程中，一种由基因控制 的主动的细胞生理性自杀行为

apoptotic nerve cells nerve cells nerve 乎甲P学 CELL DEATH MATCHES nerve NUMBER OF cel一 NERVE CELLS axon TO NUMBER OF TARGET CELLS survival factor target cells released by target cells

Morphological and biochemical characteristics of apoptosis Morphologi changes Early Chromosome condensation, cell body shrink Later: Blebbing and Nucleus and cytoplasm fragment- Apoptotic bodies At last: Phagocytosed Mild convolution Nuclear fragmentation compaction and Apoptotic phagocytic segregation Blebbing cell Condensation of Cell fragmentation

Morphological and biochemical characteristics of apoptosis  Morphologi changes: Early : Chromosome condensation, cell body shrink Later : Blebbing and Nucleus and cytoplasm fragment— Apoptotic bodies At last: Phagocytosed