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真核延伸因子-2(eEF2):其调节和肽链延伸。

Eukaryotic elongation factor-2 (eEF2): its regulation and peptide chain elongation.

机构信息

N.T Lab-I, National Dairy Research Institute, Karnal, Haryana, India.

出版信息

Cell Biochem Funct. 2011 Apr;29(3):227-34. doi: 10.1002/cbf.1740. Epub 2011 Mar 10.

Abstract

Regulation at the level of translation in eukaryotes is feasible because of the longer lifetime of eukaryotic mRNAs in the cell. The elongation stage of mRNA translation requires a substantial amount of energy and also eukaryotic elongation factors (eEFs). The important component of eEFs, i.e. eEF2 promotes the GTP-dependent translocation of the nascent protein chain from the A-site to the P-site of the ribosome. Mostly the eEF2 is regulated by phosphorylation and dephosphorylation by a specific kinase known as eEF2 kinase, which itself is up-regulated by various mechanisms in the eukaryotic cell. The activity of this kinase is dependent on calcium ions and calmodulin. Recently it has been shown that the activity of eEF2 kinase is regulated by MAP kinase signalling and mTOR signalling pathway. There are also various stimuli that control the peptide chain elongation in eukaryotic cell; some stimuli inhibit and some activate eEF2. These reports provide the mechanisms by which cells likely serve to slow down protein synthesis and conserve energy under nutrient deprived conditions via regulation of eEF2. The regulation via eEF2 has also been seen in mammary tissue of lactating cows, suggesting that eEF2 may be a limiting factor in milk protein synthesis. Regulation at this level provides the molecular understanding about the control of protein translocation reactions in eukaryotes, which is critical for numerous biological phenomenons. Further the elongation factors could be potential targets for regulation of protein synthesis like milk protein synthesis and hence probably its foreseeable application to synthetic biology.

摘要

真核生物翻译水平的调控是可行的,因为真核生物 mRNA 在细胞中的寿命更长。mRNA 翻译的延伸阶段需要大量的能量和真核延伸因子(eEFs)。eEFs 的重要组成部分,即 eEF2,促进新生蛋白链从核糖体的 A 位到 P 位的 GTP 依赖性易位。eEF2 主要通过特定的激酶(称为 eEF2 激酶)的磷酸化和去磷酸化来调节,该激酶本身通过真核细胞中的各种机制上调。该激酶的活性依赖于钙离子和钙调蛋白。最近的研究表明,eEF2 激酶的活性受到 MAP 激酶信号和 mTOR 信号通路的调节。也有各种刺激物控制真核细胞中肽链的延伸;一些刺激物抑制,而另一些刺激物激活 eEF2。这些报告提供了细胞在营养缺乏条件下通过调节 eEF2 来减缓蛋白质合成和节约能量的机制。eEF2 的调节也在泌乳奶牛的乳腺组织中观察到,这表明 eEF2 可能是乳蛋白合成的限制因素。这种在翻译水平上的调控为控制真核生物中蛋白质易位反应提供了分子理解,这对许多生物学现象至关重要。此外,延伸因子可能是蛋白质合成(如乳蛋白合成)的潜在调节靶点,因此可能在合成生物学中有其可预见的应用。

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