Recruitment and actions of the protein kinase ERK2 in transcription complexes at the serum response element

血清反应元件转录复合物中蛋白激酶 ERK2 的募集和作用

• 批准号: BB/D019117/1
• 负责人: Peter Shaw
• 金额: $ 49.18万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD019117%2F1
• 关键词: Recruitment; actions; protein; kinase; ERK2

Most animals are made up of many cells, all of which originate from a fertilised egg. As the cells in an embryo divide again and again they also change their characteristics (differentiate) so that different types of cells develop forming muscles, nerves, bones, blood and all the other tissues in the animal's body. The processes of cell division and specialisation (or development) follow blueprints contained in the animal's genetic material, the DNA in the nucleus of each cell. For cells to survive, to divide, to differentiate and even to die, information in the DNA has to be accessed, decoded and transmitted to the rest of the cell and even to other cells, rather like information on a hard disk has to be accessed for a computer to function properly. The DNA also has to be copied and passed on to each daughter cell. This research proposal addresses the mechanism by which information in the DNA is accessed. The information is packaged into units called genes of which there are about 30,000 in human cells. Genes are read (transcribed) by enzymes called RNA polymerases and these must be brought to each gene at the right time so that the flow of information is orchestrated. Control of RNA polymerases relies on other proteins called transcription factors that can select specific genes and activate them (or repress them) in response to signals from inside or outside the cell. This is the fundamental process to be studied in the research described here. It focuses on a single transcription factor called Elk-1 and how signals transmitted through the cell activate and later down-regulate Elk-1 to switch on and off a subset of genes. It is a model system from which we have already learnt much about gene transcription in general, but Elk-1 and its closest relatives are particularly important in the control of genes involved in cell proliferation and survival as well as in nerve cell functions. By continuing to study Elk-1 we hope to understand one day in molecular terms exactly how genes are regulated and also the contribution of Elk-1 to the processes of learning and memory.

大多数动物是由许多细胞组成的，所有这些细胞都来自受精卵。当胚胎中的细胞一次又一次分裂时，它们也会改变其特征（分化），从而发育出不同类型的细胞，形成肌肉、神经、骨骼、血液和动物体内的所有其他组织。细胞分裂和特化（或发育）的过程遵循动物遗传物质中包含的蓝图，即每个细胞核中的DNA。细胞要生存、分裂、分化甚至死亡，DNA中的信息必须被访问、解码并传输到细胞的其他部分，甚至其他细胞，就像计算机必须访问硬盘上的信息才能正常工作一样。DNA也必须被复制并传递到每个子细胞。这项研究计划解决了DNA中信息被访问的机制。这些信息被打包成称为基因的单位，人类细胞中大约有30，000个基因。基因被称为RNA聚合酶的酶读取（转录），这些酶必须在正确的时间被带到每个基因上，以便信息的流动得到协调。RNA聚合酶的控制依赖于其他称为转录因子的蛋白质，这些转录因子可以选择特定的基因并激活它们（或抑制它们）以响应来自细胞内外的信号。这是在这里描述的研究中要研究的基本过程。它专注于一个名为Elk-1的单一转录因子，以及通过细胞传输的信号如何激活并随后下调Elk-1以打开和关闭一个基因子集。这是一个模型系统，我们已经从中了解了很多关于基因转录的一般知识，但Elk-1及其最接近的亲属在控制涉及细胞增殖和存活以及神经细胞功能的基因方面特别重要。通过继续研究Elk-1，我们希望有一天能从分子水平上确切地了解基因是如何调控的，以及Elk-1对学习和记忆过程的贡献。

项目成果

Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1.

• DOI: 10.1093/nar/gkn099
• 发表时间: 2008-05
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Zhang HM;Li L;Papadopoulou N;Hodgson G;Evans E;Galbraith M;Dear M;Vougier S;Saxton J;Shaw PE
• 通讯作者: Shaw PE

ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1.

• DOI: 10.1093/nar/gkt837
• 发表时间: 2013-12
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Galbraith MD;Saxton J;Li L;Shelton SJ;Zhang H;Espinosa JM;Shaw PE
• 通讯作者: Shaw PE

The Amino-terminal Domain of the Androgen Receptor Co-opts Extracellular Signal-regulated Kinase (ERK) Docking Sites in ELK1 Protein to Induce Sustained Gene Activation That Supports Prostate Cancer Cell Growth.

• DOI: 10.1074/jbc.m116.745596
• 发表时间: 2016-12-09
• 期刊: The Journal of biological chemistry
• 作者: Rosati R;Patki M;Chari V;Dakshnamurthy S;McFall T;Saxton J;Kidder BL;Shaw PE;Ratnam M
• 通讯作者: Ratnam M

Molecular dynamics simulations and in silico peptide ligand screening of the Elk-1 ETS domain.

Elk-1 ETS 结构域的分子动力学模拟和计算机肽配体筛选。

• DOI: 10.1186/1758-2946-3-49
• 发表时间: 2011
• 期刊: Journal of cheminformatics
• 影响因子: 8.6
• 作者: Hussain A