Arginine methylation and its influence on transcription and genotoxic stress

精氨酸甲基化及其对转录和基因毒性应激的影响

• 批准号: BB/P008232/1
• 负责人: Karim Malik
• 金额: $ 47.41万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP008232%2F1
• 关键词: Arginine; methylation; its; influence; transcription

Integrity of the genetic material contained in animal cells, together with appropriate use of the information contained therein, is absolutely indispensable for the development of different types of cells that make up a normal and healthy living organism. Our DNA contains over 20,000 units of information for making proteins. These units are known as genes, and as we develop, these genes (and proteins) need to be switched on and switched off in cell-type specific ways, thereby enabling each different type of cell to survive, grow and take on its allotted task in a multicellular organism, such as becoming nerve cells, or, alternatively, blood cells. This work seeks to examine how a protein involved in switching on genes, named BRD4, might select certain genes in certain cell-types in order to help different groups of cells attain their unique identity, thereby enabling their appropriate function. We believe that this is made possible by BRD4 gaining different marks on it that enable it to form different complexes with other proteins. We aim to determine the nature of these marks and the interactions that they control.Another key function that BRD4 performs in cells is that it acts as a shield for the genetic material to protect it from damage. Possible sources of damage include ageing and radiation. We think that this too might depend on marks on BRD4. This will also be investigated in our study.

动物细胞中所含遗传物质的完整性，以及对其中所含信息的适当利用，对于构成正常和健康生物体的不同类型细胞的发育是绝对不可或缺的。我们的DNA包含超过20，000个单位的信息，用于制造蛋白质。这些单位被称为基因，随着我们的发展，这些基因（和蛋白质）需要以细胞类型特定的方式打开和关闭，从而使每种不同类型的细胞能够生存，生长并在多细胞生物体中承担其分配的任务，例如成为神经细胞，或者，血细胞。这项工作旨在研究一种名为BRD4的蛋白质如何参与基因的开关，如何选择某些细胞类型中的某些基因，以帮助不同的细胞群获得其独特的身份，从而使它们能够发挥适当的功能。我们认为，这是由于BRD4在其上获得了不同的标记，使其能够与其他蛋白质形成不同的复合物。我们的目标是确定这些标记的性质以及它们控制的相互作用。BRD 4在细胞中执行的另一个关键功能是它作为遗传物质的屏障，以保护其免受损害。可能的损害来源包括老化和辐射。我们认为这也可能取决于BRD4上的标记。这也将在我们的研究中进行调查。

项目成果

Transcriptomic Analyses of MYCN-Regulated Genes in Anaplastic Wilms' Tumour Cell Lines Reveals Oncogenic Pathways and Potential Therapeutic Vulnerabilities.

• DOI: 10.3390/cancers13040656
• 发表时间: 2021-02-06
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Szemes M;Melegh Z;Bellamy J;Park JH;Chen B;Greenhough A;Catchpoole D;Malik K
• 通讯作者: Malik K

Wnt signalling is a major determinant of neuroblastoma cell lineages

• DOI: 10.1101/506980
• 发表时间: 2018-12
• 期刊: bioRxiv
• 作者: M. Szemes;A. Greenhough;K. Malik

A Wnt-BMP4 signalling axis induces MSX and NOTCH proteins and promotes growth suppression and differentiation in neuroblastoma

Wnt-BMP4 信号轴诱导 MSX 和 NOTCH 蛋白并促进神经母细胞瘤的生长抑制和分化

• DOI: 10.1101/2020.02.07.938654
• 发表时间: 2020
• 作者: Szemes M

Wnt signalling drives context-dependent differentiation or proliferation in neuroblastoma

• DOI: 10.1101/236745
• 发表时间: 2018-01
• 期刊: bioRxiv
• 作者: M. Szemes;A. Greenhough;Z. Melegh;Sally Malik;A. Yuksel;D. Catchpoole;Kelli Gallacher;M. Kollareddy;J. H. Park;K. Malik

Wnt Signalling Drives Context-Dependent Differentiation or Proliferation in Neuroblastoma.

• DOI: 10.1016/j.neo.2018.01.009
• 发表时间: 2018-04
• 期刊: Neoplasia (New York, N.Y.)
• 作者: Szemes M;Greenhough A;Melegh Z;Malik S;Yuksel A;Catchpoole D;Gallacher K;Kollareddy M;Park JH;Malik K
• 通讯作者: Malik K