Identification of elF3e-Int6p targets in Stress in Pombe

粟酒应激中 elF3e-Int6p 靶点的鉴定

• 批准号: 7113483
• 负责人: SABRINA K HAWTHORNE
• 金额: $ 0.67万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113483
• 关键词: Schizosaccharomyces pombe; environmental adaptation; environmental stressor; fungal genetics; genetic screening; genetic translation; messenger RNA; osmotic pressure; postdoctoral investigator; proteomics; stress; temperature; translation factor

DESCRIPTION (provided by applicant): The machinery of translation is subject to regulation in situations of cellular determination, rapid response, and cellular stress. Translational initiation involves the recruitment of the 40S ribosomal subunit through elF2, elF3, and elF4 followed by the assembly of the function 80 complex. Dr. Dieter Wolf's lab identified distinct elF3 complexes containing either elF3m/Csn7B or the related elF3e/lnt6p (Zhou et al., 2005). Further studies support a hypothesis for the use of alternate versions of these elF3 complexes under conditions of stress in S. pombe. Using fission yeast as a model the experiments described in this proposal will test this hypothesis through identification and validation of translational targets of lnt6p-elF3e under conditions of stress. Candidates will be verified and analyzed by genetic and biochemical approaches to determine mechanisms of translational repression and activation. Significantly, reduced INT6 expression is also found in 30-40% of human breast cancers, suggesting a close link between loss of INT6 expression and breast cancer development. The proposed research explores a novel role of INT6 in tumorigenesis through basic studies of its involvement in stress-regulated translation.

描述（由申请人提供）：在细胞测定，快速反应和细胞应激的情况下，翻译的机制受到调节。翻译起始涉及通过ELF2，ELF3和ELF4募集40S核糖体亚基，然后组装功能80复合物。 Dieter Wolf博士的实验室确定了包含ELF3M/CSN7B或相关ELF3E/LNT6P的不同ELF3复合物（Zhou等，2005）。进一步的研究支持在pombe的压力条件下使用这些ELF3复合物的替代版本的假设。使用裂变酵母作为模型，本提案中描述的实验将通过在压力条件下识别和验证LNT6P-FELF3E的平移目标来检验该假设。候选人将通过遗传和生化方法来验证和分析，以确定转化抑制和激活的机制。值得注意的是，在30-40％的人乳腺癌中也发现了INT6表达降低，这表明INT6表达和乳腺癌发展之间的损失之间存在密切联系。拟议的研究通过基础研究探讨了INT6在肿瘤发生中的新作用，其参与应力调节翻译。