CCR4-NOT COACTIVATOR'S POST-TRANSCRIPTION FUNCTIONS

CCR4-NOT 共激活剂的转录后功能

• 批准号: 7960281
• 负责人: MARK Jude SWANSON
• 金额: $ 2.66万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960281
• 关键词: Amino Acids; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Environment; Eukaryota; Funding; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Genetic Transcription; Goals; Grant; Human; Hypoxia; Institution; Mammalian Cell; Memory; Messenger RNA; Mus; Nebraska; Pattern; Proteins; Research; Research Personnel; Resources; Role; Saccharomyces cerevisiae; Signal Transduction; Source; Starvation; System; Transcription Coactivator; Transcription Initiation; Translations; United States National Institutes of Health; Work; Yeasts; aminoacid biosynthesis; functional genomics; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. All cells respond to changes in their environment by altering patterns of gene expression. Gene regulation in eukaryotes begins at the initiation of transcription and continues through export and translation of messenger RNAs. In the yeast Saccharomyces cerevisiae, starvation for amino acids generates a signal that leads to an increase in the level of Gcn4p, a transcriptional activator protein. Gcn4p regulates the expression of over 500 genes, including those involved in amino acid biosynthesis. Thus, yeast cells that cannot obtain amino acids from their environment produce their own. Mechanisms by which Gcn4p activates its target genes have been well studied, but it is not clear how these genes are repressed after starvation conditions are relieved. Gcn4p requires the CCR4-NOT co-activator complex for full target gene expression. However, CCR4-NOT also possesses activities involved in the destruction rather than the creation of mRNAs. The overall goal of this research is to determine the exact post-transcriptional role(s) of CCR4-NOT in Gcn4p target gene expression. The mechanisms by which mammalian cells adapt to amino acid limitation are very similar to those in yeast, and they have been implicated in memory formation in mice and survival of hypoxic conditions by human tumors. Since the CCR4-NOT complex is also conserved, results from the proposed work are applicable to studies in mammalian systems.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 所有细胞都通过改变基因表达模式来应对环境的变化。真核生物中的基因调控开始于转录的起始，并通过信使RNA的输出和翻译继续。在酿酒酵母中，氨基酸饥饿产生一个信号，导致Gcn 4p（一种转录激活蛋白）水平的增加。Gcn 4p调控500多个基因的表达，包括那些参与氨基酸生物合成的基因。因此，不能从环境中获得氨基酸的酵母细胞会产生自己的氨基酸。Gcn 4p激活其靶基因的机制已经得到了很好的研究，但目前还不清楚这些基因是如何在饥饿条件解除后被抑制的。Gcn 4p需要CCR 4-NOT共激活因子复合物以实现完整的靶基因表达。然而，CCR 4-NOT也具有参与破坏而不是创建mRNA的活动。本研究的总体目标是确定CCR 4-NOT在Gcn 4p靶基因表达中的确切转录后作用。哺乳动物细胞适应氨基酸限制的机制与酵母中的机制非常相似，并且它们与小鼠的记忆形成和人类肿瘤在缺氧条件下的存活有关。由于CCR 4-NOT复合物也是保守的，因此拟议工作的结果适用于哺乳动物系统的研究。