TRRAP 在 p53 介导的 mdm2 转录中的作用-猫眼课题宝

TRRAP 在 p53 介导的 mdm2 转录中的作用

批准号：

7229476

负责人：

STEVEN B. MCMAHON

金额：

$26.16万

依托单位：

THOMAS JEFFERSON UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2003

资助国家：

美国

项目状态：

已结题

起止时间：

2003-07-01 至 2010-04-30

来源：

https://reporter.nih.gov/project-details/7229476

关键词：

Acetyltransferase Address Apoptosis Binding Binding Sites Biochemical Cell Cycle Cell Cycle Arrest Cells Cellular Stress Chromatin Chromatin Structure Complex DNA Binding DNA Damage DNA Repair DNA-Directed RNA Polymerase Data Dependence Depth Elements Enzymes Event Family Feedback Gene Targeting Genes Genetic Genetic Transcription Goals Histone Acetylation Histone Deacetylase Histones Holoenzymes Human In Vitro Individual Lesion Lysine Malignant Neoplasms Maps Mediating Molecular Mutate Normal Cell Nucleosomes Numbers Oncogenes Pathway interactions Physiological Play Polymerase Positioning Attribute Post-Translational Protein Processing Protein Binding Protein Overexpression Protein p53 Proteins Reaction Recruitment Activity Reporting Role Structure Study Section TATA-Binding Protein Associated Factors TATA-Box Binding Protein TP53 gene TRRAP gene TRRAP protein Tail Therapeutic Intervention Transactivation Transcriptional Activation Transcriptional Regulation cancer cell cofactor design histone acetyltransferase in vivo insight multicatalytic endopeptidase complex promoter repaired response transcription factor tumor ubiquitin-protein ligase

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DESCRIPTION (provided by applicant): The p53 tumor suppressor regulates the cellular response to genetic damage through its function as a sequence-specific transcription factor. Among the most well-characterized transcriptional targets of p53 is the mdm2 oncogene, which is overexpressed in a number of common human cancers. Transcriptional activation of mdm2 is critical in the p53 pathway because its protein product marks p53 for proteosome-mediated degradation, thereby providing a negative feedback loop. We have shown that recruitment of the ATM-related TRRAP protein is essential for p53-mediated activation of mdm2 transcription. TRRAP is a component of several, multi-protein acetyltransferase complexes implicated in both transcriptional regulation and DNA repair. Among the goals of this study are: a.) defining which of the distinct TRRAP complexes is required for p53 function, b.) assessing other p53 target genes for TRRAP dependence, c.) defining the molecular consequences of TRRAP recruitment to the mdm2 promoter, d.) mapping the unique elements within the mdm2 promote which confer its TRRAP dependence. Understanding the role that the TRRAP complexes play in the biochemical activity of p53 should provide us with a deeper molecular insight into the pathway mutated most frequently in human cancer.

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