Deciphering sumoylation-dependent signalling through systematic loss-of-function analysis in C. elegans

通过线虫的系统功能丧失分析破译苏素化依赖性信号传导

• 批准号: G0600127/1
• 负责人: Gino Poulin
• 金额: $ 107.31万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600127%2F1
• 关键词: Deciphering; sumoylation; dependent; signalling; through

Proteins are often active in multiprotein complexes and have to be localised into the appropriate cellular compartments. In many cases, proteins are modified and these modifications can regulate their stability, promote physical interactions and specify their localisation, for example. One such modification is sumoylation; where a short polypeptide (SUMO) is transferred onto a protein. The added SUMO on a protein leads to novel interactions or relocalisation. Sumoylation has been found involved in Huntington‘s disease and viral infection. Some viruses inhibit sumoylation to create a better environment for their multiplication. I discovered that in absence of SUMO, oncogenic pathways, pathways involved in cancer, are more active. I will investigate sumoylation in vivo by systematic identification of the co-factors involved in this process using C. elegans as a model. The advantages of this model are that the sumoylation process is conserved in C. elegans, and there is a technology called RNA interference (RNAi) that inactivates gene expression. We have built an RNAi library that individually inactivates all the predicted genes of the C. elegans genome. Using this technology I will identify the genes cooperating and regulating the sumoylation process. I will also use classical biochemistry and fluorescence imaging to visualise sub-cellular localisation.

蛋白质在多蛋白复合体中通常是活跃的，必须定位到适当的细胞隔间中。例如，在许多情况下，蛋白质被修饰，这些修饰可以调节它们的稳定性，促进物理相互作用，并指定它们的定位。一种这样的修饰是SUMO化；在这种修饰中，一个短的多肽(SUMO)被转移到蛋白质上。蛋白质上添加的相扑导致了新的相互作用或重新定位。苏莫化已被发现与亨廷顿病和病毒感染有关。一些病毒抑制相扑作用，为它们的繁殖创造更好的环境。我发现，在没有相扑的情况下，致癌途径，即与癌症有关的途径，更活跃。我将以秀丽线虫为模型，通过系统地鉴定参与这一过程的辅助因素，来研究体内的相思作用。这个模型的优点是线虫中的相加过程是保守的，并且有一种称为RNA干扰(RNAi)的技术可以使基因表达失活。我们已经建立了一个RNAi文库，它可以单独使线虫基因组的所有预测基因失活。使用这项技术，我将识别协同和调节相扑过程的基因。我还将使用经典的生物化学和荧光成像来可视化亚细胞定位。