【文章內(nèi)容簡(jiǎn)介】
2 12 4 大鼠 十二脂腸隱窩細(xì)胞 內(nèi)釉質(zhì)上皮細(xì)胞 肝細(xì)胞 三、細(xì)胞周期各時(shí)相的動(dòng)態(tài)變化 ? Interphase ? G1 (1st gap) G1期 ? S phase S期 ? G2 (2nd gap) G2期 ? Mitotic Phase( M 期, 有絲分裂期) ? Mitosis (nuclear division) ? Cytokinesis (cytoplasmic division) 1. G1 stage ( The first gap , DNA合成前期) ? Much longer than other phases ? The growth phase: Cells increase in size , doubles its anelles ? produce RNA and synthesize protein for DNA synthesis. ? pro phosphorilation ? restriction point ? TG1 較其他時(shí)期 長(zhǎng) ? 細(xì)胞體積增大 ? 合成各種 RNA和 蛋白質(zhì) ? 蛋白質(zhì)的磷酸化作用加強(qiáng)( 與 DNA合成啟動(dòng)相關(guān)) ? 限制點(diǎn) G1向 S期轉(zhuǎn)變的 pro:觸發(fā)蛋白 、鈣調(diào)蛋白、 cyc 合成與 DNA復(fù)制有關(guān)的酶 該期的中心任務(wù)是為 S期的 DNA合成做準(zhǔn)備 組蛋白、非組蛋白、激酶磷酸化、 Rb 觸發(fā)蛋白: 一類不穩(wěn)定蛋白質(zhì),只有當(dāng)含量達(dá)到臨界值時(shí),才可轉(zhuǎn)向 DNA復(fù)制方向。 鈣調(diào)蛋白: 核內(nèi) Ca2+受體,調(diào)節(jié) Ca2+濃度;在 G1末達(dá)峰值,促進(jìn) G1向 S轉(zhuǎn)變。 細(xì)胞周期蛋白 (cyclin): 一類隨細(xì)胞周期的變化呈周期性的出現(xiàn)與消失的蛋白質(zhì),在細(xì)胞周期的不同階段表達(dá),發(fā)揮不同的調(diào)控作用。它可以與細(xì)胞周期基因的產(chǎn)物 ( p34cdc2) 結(jié)合并調(diào)節(jié)其活性,是 MPF的調(diào)節(jié)亞基。 限制點(diǎn) (restriction point ) ? 限制點(diǎn)存在于 G1期晚期,是對(duì)一些環(huán)境因素的敏感點(diǎn),可限制正常細(xì)胞通過周期。是控制細(xì)胞增殖的關(guān)鍵。 ? 是哺乳動(dòng)物細(xì)胞周期 G1期控制進(jìn)入 S期的調(diào)節(jié)點(diǎn),相當(dāng)于酵母的 START點(diǎn)。 proliferation type of cell (組織細(xì)胞的增殖類型 ) Three categories of cells in multicellular animals ? Cycling cell ? G0 phase cell ? Terminally differentiated cells 周期性細(xì)胞 (cycling cell ) ? Cycling cell : Some cell types progress continuously through the cell cycle to acmodate cell or tissue growth. ? 周期性細(xì)胞 :是指在細(xì)胞周期中連續(xù)運(yùn)轉(zhuǎn)的細(xì)胞 ,又稱為連續(xù)分裂細(xì)胞或可育細(xì)胞 , 如表皮生發(fā)層細(xì)胞 ( basal cell layer) 、 部分骨髓細(xì)胞 (bone marrow stem cells)。 靜止期細(xì)胞( quiescent cell) ? 暫不增殖細(xì)胞 :指的是暫時(shí)離開細(xì)胞周期,停止細(xì)胞分裂,去執(zhí)行一定的生物學(xué)功能,但在適當(dāng)?shù)拇碳は驴芍匦逻M(jìn)入細(xì)胞周期的細(xì)胞,又稱為 G0期細(xì)胞 或 休眠細(xì)胞 ,如淋巴細(xì)胞、肝、腎細(xì)胞等。 ? quiescent cell: Some living cells exit G1 to enter a quiescent stage of the cycle called G0, where they remain metabolically active but no longer proliferate unless called on to do so by appropriate extracellular signals. 終末分化細(xì)胞 (Terminally differentiated cells) ? 終末分化細(xì)胞: 指不可逆地脫離細(xì)胞周期,喪失分裂能力,保持生理機(jī)能活動(dòng)的細(xì)胞,又稱終端細(xì)胞,如神經(jīng)、肌肉、多形核細(xì)胞等。 ? Terminally differentiated cells: Some G0 cells NEVER divide again and are referred to as being TERMINALLY DIFFERENTIATED. (. nerve cells) 各增殖類型的代表組織細(xì)胞 2. S期( DNA合成期) ⑴ DNA復(fù)制 (早與晚 ) ① GCAT ② 常 —— 異染色質(zhì) —— inactive X ⑵ 組蛋白 等的合成 ⑶ 中心粒復(fù)制 A PULSELABELING EXPERIMENT 1. Feed radioactive thymidine (T*) to cells growing in culture. 2. After 30 minutes, wash unincorporated T* out of cell culture. 3. Spread out cells and lay xray film over them. Conclusion ? DNA的合成與組蛋白的合成強(qiáng)度保持時(shí)間上的同步,密度上的相應(yīng),而使新合成的 DNA得以及時(shí)包裝成核小體,二者保持一種聯(lián)動(dòng)關(guān)系。 中心粒的發(fā)育過程(中心體周期) ? 中心粒在 G1中期以后開始分開。 ? 中心粒在 S期復(fù)制:兩個(gè)中心粒各產(chǎn)生了一個(gè)新的中心粒。 ? 中心體在 G2晚期至 M早期(前期),長(zhǎng)大并向細(xì)胞兩極移動(dòng)。 ? cell growth continues. ? MPF is synthesized. ? proteins are synthesized in preparation for mitosis. ? Centrosome grows in G2 stage and begin to move to the two poles of the cell. ? Relatively short. 1. 細(xì)胞繼續(xù)長(zhǎng)大。 2. 合成成熟促進(jìn)因子( MPF) —— 準(zhǔn)備進(jìn)入 M期。 3. 合成微管蛋白等 ,為 M期紡錘體準(zhǔn)備。 4. 中心體在 G2期長(zhǎng)大, G2晚期開始向細(xì)胞兩極移動(dòng)。 5. 持續(xù)時(shí)間較短。 G2 phase 染色質(zhì)凝集,紡錘體形成,收縮環(huán)出現(xiàn), 遺傳物質(zhì)和細(xì)胞內(nèi)其他物質(zhì)分配給子細(xì)胞 ? M期即細(xì)胞分裂期 ? M phase is also called mitosis. ? Occurs after G2 phase and before next G1 phase ? Consists of nuclear division and cytoplasmic division M phase (一 )細(xì)胞周期的蛋白因子調(diào)控 1. 細(xì)胞周期蛋白 (cyclin) 2. 成熟促進(jìn)因子 (maturation promoting factor) 3. 生長(zhǎng)因子 (growth factor) 4. 抑素 (chalone) 5. RNA剪接因子 SR蛋白及 SR蛋白特異的 激酶 (二 )細(xì)胞周期的基因調(diào)控 四、細(xì)胞周期的調(diào)控 1. Cyclins (細(xì)胞周期蛋白 ) 1. What are cyclins? 2. How does cyclin degrade? 3. How many kinds cyclins are there? 4. When and how does CDK active? ? The concentration of mitotic cyclins (. cyclin B) and MPF activity increase as cells enter mitosis and then falls rapidly during late anaphase. ? The concentration of the MPF kinase (the Cdk) does not change during the course of the cell cycle. Only the activity changes. ? The cyclical expression of the mitotic cyclin is the result of proteolysis. Cyclin 的發(fā)現(xiàn): ? 1983, sea urchin embryo. ?Tim Hunt 從分裂的海膽卵受精及卵裂過程中的生化研究中發(fā)現(xiàn) the mitotic cyclins。 ?發(fā)現(xiàn)濃度周期性變化的蛋白質(zhì) —— 細(xì)胞周期素( cyclins) ?In synchronously dividing cells of the sea urchin embryo, the concentration of mitotic cyclins (. cyclin B) and MPF activity increase as cells enter mitosis and then falls rapidly during late anaphase. Periodic Expression of Cyclins 細(xì)胞周期蛋白 (Cyclin) 細(xì)胞周期蛋白 :在細(xì)胞周期中濃度有規(guī)律地升高和降低的 蛋白質(zhì) ,它可激活周期蛋白依賴性激酶,從而調(diào)控細(xì)胞周期的進(jìn)程。 ? Cyclins are proteins formed and degraded during each cell cycle. Periodic protein degradation is an important control mechanism of the cell cycle. 不同細(xì)胞周期蛋白的功能 ? G1期周期蛋白: Cyclin C、 D、 E等 ?Cyclin D –CDK4/6 -- pass R point ?Cyclin E CDK2 -- G1/S 該復(fù)合物為 S期啟動(dòng)所必需。 CyclinE的抗體能使細(xì)胞停滯于 G1期。 ? CycACDK2與 DNA復(fù)制有關(guān),也與 G2/M有關(guān) ? M期周期蛋白: CyclinA、 B ?CycACDK2 ?CycBCDK1 G2/M 這些周期蛋白有的只在 G1期表達(dá)并只在 G1/S期轉(zhuǎn)化過程中執(zhí)行調(diào)節(jié)功能 , 所以