Characterization of a Potential Nuclear Protein Depot

潜在核蛋白库的表征

• 批准号: 6541688
• 负责人: GERD G MAUL
• 金额: $ 33.36万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6541688
• 关键词: biological signal transduction; cell nucleus; cytoprotection; cytotoxicity; genetic transcription; microarray technology; nucleoproteins; organelles; oxidative stress; polymerase chain reaction; protein localization; protein protein interaction; protein structure function

DESCRIPTION (provided by applicant): Specific nuclear domains named ND10, PML bodies or PODs have reached prominence because proteins contained in these structures are directly or indirectly associated with specific diseases such as acute promyelocytic leukemia, various viral infections, cadmium and arsenic exposure and other environmental toxins. In addition, cellular regulatory loops induced by interferon and thermal stress are correlated with recruitment to or release of regulatory proteins like PML, Daxx and Sp100 from ND10 However, none of the encompassing transcriptional changes appear to occur directly at these nuclear sites. We therefore hypothesize that ND 10 function as nuclear depots, thus separating the functional site of the ND 10-associated proteins from that of their highest aggregation at ND 10. To determine what functions are controlled through release or recruitment of ND 10-associated proteins and what the benefits are to the cell in combating the induced stress, we plan to identify and characterize the protein composition of ND 10, determine which proteins regulate ND 10 dispersion and analyze the regulatory mechanisms underlying the segregation and dispersion of specific proteins. We will establish the functions of ND10 and their associated proteins by testing for the effects of loss and regulated change of specific ND10-associated proteins on the cells transcriptional profile using knock-out cells and regulatable revertants. We will define the mechanisms used by global effectors such as thermal stress, cadmium and arsenic exposure that activate the regulatory pathways controlled at ND 10. Specifically, we will define the biological significance of the regulated sequestration or release of ND 10-associated proteins in the defense of the cell from toxins and stress.

描述（由申请人提供）：称为ND10，PML身体或POD的特定核域已达到突出，因为这些结构中包含的蛋白质直接或间接与特定疾病（例如急性前临床前白血病，各种病毒感染），CADMIUM和CADMIUM，CADMIUM和ARSENIC SPARIC曝光和其他环境毒素有关。此外，由干扰素诱导的细胞调节环和热应力与募集或释放ND10的调节蛋白（如PML，DAXX和SP100）相关，但是，围绕转录变化的任何一种都没有直接发生在这些核地点。 We therefore hypothesize that ND 10 function as nuclear depots, thus separating the functional site of the ND 10-associated proteins from that of their highest aggregation at ND 10. To determine what functions are controlled through release or recruitment of ND 10-associated proteins and what the benefits are to the cell in combating the induced stress, we plan to identify and characterize the protein composition of ND 10, determine which proteins regulate ND 10分散和分析特定蛋白质隔离和分散的基础的调节机制。我们将通过测试使用基因敲除细胞和可调节的恢复物的转录细胞对细胞转录曲线的转录曲线变化的影响，从而确定ND10及其相关蛋白的功能。我们将定义全球效应子（例如热应力，镉和砷暴露）使用的机制，这些机制激活了ND 10时控制的调节途径。具体而言，我们将定义调节的隔离或释放ND 10相关蛋白质释放的生物学意义。