Modelization of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive
Modelization of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive
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海胆受精后蛋白质合成调节的模型显示需要两个过程：eIF4E:4E-BP 复合物的不稳定和 4E-BP 降解机制的巨大刺激，两者都是雷帕霉素敏感的
作者：
Sébastien Laurent;A. Richard;O. Mulner;J. Morales;D. Flament;V. Glippa;Jérémie Bourdon;Pauline Gosselin;A. Siegel;P. Cormier;R. Bellé
海胆卵的受精涉及与翻译起始抑制剂4 E-BP的量减少相关的蛋白质合成增加。建立了一个高度简单的蛋白质合成调控反应模型，并用于模拟受精后一段时间内观察到的4 E-BP总量的生理变化。我们的研究证明，在受精时发生的两个变化是必要的，以适应实验数据。第一个变化是eIF 4 E：4 E-BP复合物的解离参数（koff 1）增加了8倍。第二个是蛋白质4 E-BP的降解机制的重要32.5倍活化。此外，这两个过程的变化应发生在受精后5分钟的时间间隔。为了验证该模型，我们检查了受精时eIF 4 E：eIF 4G复合物浓度预测增加4.2倍的动力学与受精后实验观察到的蛋白质合成增加相匹配（6.6倍，SD = 2.3，n = 8）。最小模型还用于模拟在雷帕霉素（一种FRAP/mTOR抑制剂）存在下受精后观察到的变化。该模型显示，eIF 4 E：4 E-BP复合物的去稳定化受到影响，令人惊讶的是，4 E-BP降解的机制也受到强烈影响，因此表明这两个过程都受到蛋白激酶FRAP/mTOR的控制。
Fertilization of sea urchin eggs involves an increase in protein synthesis associated with a decrease in the amount of the translation initiation inhibitor 4E-BP. A highly simple reaction model for the regulation of protein synthesis was built and was used to simulate the physiological changes in the total 4E-BP amount observed during time after fertilization. Our study evidenced that two changes occurring at fertilization are necessary to fit with experimental data. The first change was an 8-fold increase in the dissociation parameter (koff1) of the eIF4E:4E-BP complex. The second was an important 32.5-fold activation of the degradation mechanism of the protein 4E-BP. Additionally, the changes in both processes should occur in 5 min time interval post-fertilization. To validate the model, we checked that the kinetic of the predicted 4.2-fold increase of eIF4E:eIF4G complex concentration at fertilization matched the increase of protein synthesis experimentally observed after fertilization (6.6-fold, SD = 2.3, n = 8). The minimal model was also used to simulate changes observed after fertilization in the presence of rapamycin, a FRAP/mTOR inhibitor. The model showed that the eIF4E:4E-BP complex destabilization was impacted and surprisingly, that the mechanism of 4E-BP degradation was also strongly affected, therefore suggesting that both processes are controlled by the protein kinase FRAP/mTOR.
影响因子：
10.5
作者：
Gingras, AC;Gygi, SP;Sonenberg, N
通讯作者：
Sonenberg, N
DOI：
10.1073/pnas.95.4.1432
发表时间：
1998-02-17
影响因子：
11.1
作者：
Burnett, PE;Barrow, RK;Sabatini, DM
通讯作者：
Sabatini, DM
真核 mRNA 帽结合复合物组装过程中的折叠转变。
影响因子：
5.6
作者：
vonderHaar,Tobias;Oku,Yuko;Ptushkina,Marina;Moerke,Nathan;Wagner,Gerhard;Gross,JohnD;McCarthy,JohnEG
通讯作者：
McCarthy,JohnEG