分子細(xì)胞生物學(xué)：21細(xì)胞增殖

1、embryonic developmentCell reproduction exists in embryonic development,pathogenesis and progression of cancer. tissue renewal , wound-healing, enterocytes blood cellsProcess? Characteristic? Regulation?Cell reproduction the most important physiology phenomenom of the cells and the organisms.Chapter2

2、1 Cell Reproduction Level AvThe definition of cell cycle and the characteristics of each phase. Level CvThe differences between the mitosis and meiosis. Level BvThe major biochemical features of the interphase.vThe major morphological features of M phase.Section I Cell CycleKEY TERMS of Section I vC

3、ell cycle 細(xì)胞增殖周期細(xì)胞增殖周期vInterphase 間期間期vMitosis 有絲分裂有絲分裂vProphase 前期前期vPrometaphase 前中期前中期vMetaphase 中期中期vAnaphase 后期后期vTelophase 末期末期vMitotic spindle 紡錘體紡錘體vKinetochore 動(dòng)粒動(dòng)粒vCytokinesis 胞質(zhì)分裂胞質(zhì)分裂vMeiosis 減數(shù)分裂減數(shù)分裂vContractile ring 收縮環(huán)收縮環(huán)Section I Cell CycleThe cycle of cell duplication and division, k

4、nown as the cell cycle.Cell cycle carrys out an orderly sequence of events.G1 phase （Gap1）G2 phase（Gap2）S phase（DNA Synthesis )Cell Cycle Includes Four Phases M phaseInterphaseCell Cycle1. G1 PhaseVigorous metabolismRNA and protein synthesis (e.g. DNA polymerase) 2. S PhaseCentrosome replicationDNA

5、replicationRNA and protein synthesis (e.g. histone)3. G2 PhaseThe content of DNA is double that of G1 phaseRNA and protein synthesis (e.g. tubulin) M Phase: Mitosis and Cytokinesis2. Cytokinesis (cytoplasmic division)The final stage of M phase, begins before mitosis ends. 1. Mitosis (nuclear divisio

6、n)Mitosis is usually accompanied bycytokinesis. movie1. ProphaseSister chromatids condenseNucleolus disappearsMitotic spindle assemblesMitosis Occurs in five stages熒光照片顯示染色體的動(dòng)粒部分熒光照片顯示染色體的動(dòng)粒部分Kinetochore is a protein complex that assemble on the centromere of each condensed chromosome. Three classes

7、 of microtubules make up the mitotic spindle. astral microtubules kinetochore (chromosomal) microtubules interpolar (overlap) microtubulescartooncartoonNuclear envelope breaksChromosomes attach to spindle microtubules2. PrometaphaseChromosomes condense extremely Chromosomes are aligned at the equato

8、r of the spindle3. MetaphaseSister chromatids separate and are pulled toward the spindle pole4. AnaphaseThe kinetochore microtubules get shorter and the spindle poles also move apartDaughter chromosomes decondense Nuclear envelope and nucleolus reassembleThe formation of two nuclei marking the end o

9、f mitosis The contractile ring begins to assemble5. TelophaseThe cytoplasm is divided in twoA contractile ring pinches the cell in two to create two daughters6. CytokinesisThe surface of a furrowActin (red) and MyosinII (green)The contractile ring divides the cell in two.Animal cells change shape du

10、ring M phase.Meiosis contrasts with MitosisMeiosis happens to diploid germ-line cells Two successive nuclear division with only one round of DNA replicationProducing four haploid cells Level AvCyclinCdk complex is the core of cell-cycle control system. Level BvThe activity of CyclinCdk complex depen

11、ds on several factors.vThe definition of cell cycle checkpoint. Level CvDifferent CyclinCdk complexes trigger different steps in the cell cycle.vThe definition of G0 phase.Section II Cell Cyle ControlKEY TERMS of Section II vCyclin 細(xì)胞周期蛋白細(xì)胞周期蛋白vCyclin-dependent kinase 細(xì)胞周期蛋白依賴性激酶細(xì)胞周期蛋白依賴性激酶vCheckpoi

12、nt 檢查點(diǎn)檢查點(diǎn)vG0 phase G0期期vAnaphase-promoting complex (APC)后期促進(jìn)復(fù)合物后期促進(jìn)復(fù)合物vCdk inhibitor protein (CKI) Cdk抑制蛋白抑制蛋白Hartwell and Nurse found a kind of kinase is the key regulator of cell cycle in the yeasts at 1970s.Fission yeastBudding yeastThe concentration of cyclin rises and falls at special times dur

13、ing the cell cycle.Hunt found Cyclin from the sea in 1980s.Cyclin: regulated subunit Cyclin-dependent kinase (Cdk): catalytic subunit The cell cycle process depends on cyclically activated CdksThe key regulator of the cell cycle is Cyclin-Cdk complex ! !Different Cyclin-Cdk complexes trigger differe

14、nt steps in the cell cycle1. The accumulation of cyclins regulates the activity of CdksCyclical changes in Cdk activity are controlled by a series of moleculars.2. The activity of the Cyclin-Cdk complexes depends on phosphorylation and dephosphorylation3. Cdk activity can be blocked by Cdk inhibitor

15、 proteins (CKIs, e.g.p21,p27)4. The activity of Cyclin-Cdk complexes depends on proteolysis The key ubiquitin ligases: APC、SCFSMG1G2* A complex network of regulatory proteins in all eukaryotes The cell-cycle control system. * The core of the cell cycle control system is Cyclin-Cdk complex.* The cell

16、-cycle control system ensures that key processes in the cycle occur in the proper sequence. Wee1cdh1Cdc20SCFAPCp16p27p21Cdc25CAKG1/S-Cdk triggersprogression through Start M-Cdks stimulate entry into mitosis S-Cdk stimulateschromosomes duplicationThe activities of cyclin-Cdk complexes rise and fall a

17、s the cell progresses through the cycle leading to cyclical changes in the phosphorylation of proteins that trigger or regulate the major events of the cell cycle.G1-Cdks stimulateentry into S phaseS-Cdk initiates the DNA replication M-Cdk drives the cell enter into prometaphase M-Cdk phosphorylates

18、 the lamin dimers and makes the nuclearenvelope breakdown M-cdkcartoonInactive APCInactive APCM-CdkM-Cdk drives the cell enter into anaphase M-Cdk triggers the separation of sister chromatids Pp53DNA Damage Can Temporarily Halt Progression Through G14. M checkpoint1.G1/S checkpoint3. G2/M checkpoint

19、2. S checkpointIs all DNA damage repaired?Is all DNA replicated?Checkpoint is a signaling mechanism to act on the Cyclin-Cdk complex and to halt the cell cycleThe cell cycle can pause temporarily until conditions are right, or withdraw from the cell cycle altogethereither temporarily in G0 phase, or

20、 permanently in the case of terminally differentiated cells.The transition from G1 to S phase offers the cell a crossroad.vCells continue proliferation: e.g. stem cellsvCells give up proliferation temporarily : e.g. liver cellsvCells give up proliferation permanently: e.g. red blood cells Normal liv

21、erRenewal liverPostoperative liverSection III Cell Cycle and Medicine Level C Cell cycle and medicineKEY TERMS of Section IIIvGrowth factor 生長因子生長因子vTumor-suppressor gene 腫瘤抑制基因腫瘤抑制基因vProto-oncogene 原癌基因原癌基因Section III Cell Cycle and MedicinePromotion of cell proliferation is benefit to tissue regenerationepidermal growth factor is applied to wound healingOveravtivity of cell-cycle control system results in excessive cell proliferation of cancerProto-oncogene: e.g. Ras, mycTumor-suppressor gene: e.g.p53, p2