Mechanisms Of RNA-Binding Protein-Mediated Apoptosis In Oral Mucositis

RNA结合蛋白介导的口腔粘膜炎细胞凋亡机制

基本信息

批准号：
8503886
负责人：
Viswanathan Palanisamy
金额：
$ 32.87万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8503886
关键词：
3&apos Untranslated Regions Adverse effects Affect Apoptosis Apoptotic BAX gene Binding Caspase Cell Death Cell Survival Cells Cellular biology Cues Cultured Cells Cytoplasm Data Development Dominant-Negative Mutation Elements Epithelial Epithelial Cells Etiology Eukaryotic Cell Event Foundations Future Gene Delivery Gene Expression Gene Expression Regulation Genes Genetic Translation Goals Growth HuR protein Human Immune Inflammation Inflammatory Inflammatory Response Interleukin-1 Interleukins Ionizing radiation Lead Mediating Messenger RNA Metabolism Methods Modeling Modification Molecular Molecular Profiling Mouth Diseases Mucositis Mus Nuclear Oral Oral mucous membrane structure PTGS2 gene Pain Pathway interactions Post-Transcriptional Regulation Post-Translational Protein Processing Process Protein Binding Protein Isoforms Proteins RNA RNA-Binding Proteins Radiation Radiation therapy Regulator Genes Reporting Research Role Signal Transduction Stress System TNF gene TNFRSF1A gene Testing Tongue Transcript Translations Vision Work adenoviral-mediated base cancer therapy chemoradiation chemotherapy cytokine in vivo mRNA Decay mRNA Expression mRNA Stability mouse model novel oral mucositis overexpression public health relevance response treatment strategy

3&apos Untranslated Regions Adverse effects Affect Apoptosis Apoptotic BAX gene Binding Caspase Cell Death Cell Survival Cells Cellular biology Cues Cultured Cells Cytoplasm Data Development Dominant-Negative Mutation Elements Epithelial Epithelial Cells Etiology Eukaryotic Cell Event Foundations Future Gene Delivery Gene Expression Gene Expression Regulation Genes Genetic Translation Goals Growth HuR protein Human Immune Inflammation Inflammatory Inflammatory Response Interleukin-1 Interleukins Ionizing radiation Lead Mediating Messenger RNA Metabolism Methods Modeling Modification Molecular Molecular Profiling Mouth Diseases Mucositis Mus Nuclear Oral Oral mucous membrane structure PTGS2 gene Pain Pathway interactions Post-Transcriptional Regulation Post-Translational Protein Processing Process Protein Binding Protein Isoforms Proteins RNA RNA-Binding Proteins Radiation Radiation therapy Regulator Genes Reporting Research Role Signal Transduction Stress System TNF gene TNFRSF1A gene Testing Tongue Transcript Translations Vision Work adenoviral-mediated base cancer therapy chemoradiation chemotherapy cytokine in vivo mRNA Decay mRNA Expression mRNA Stability mouse model novel oral mucositis overexpression public health relevance response treatment strategy

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项目摘要

DESCRIPTION (provided by applicant): Our proposed research will determine the post-transcriptional regulation that changes oral mucositis development and progression via RNA binding proteins (RBPs), which are critical regulators of gene expression in most eukaryotic cells. These proteins influence key aspects of mRNA metabolism including nuclear transit and cytoplasmic export, transport, storage, translation, and turnover. First, among various RNA- binding proteins, HuR is a prominent protein influencing cellular response to stress, proliferative signals, immune triggers, and developmental cues. HuR encodes many inflammation and apoptosis-related mRNAs including cytokines, interleukins and pro-apoptotic factors which are downstream targets we intend to study. Given HuR's influence on expression of these key modulators, we are intrigued about HuR protein binding mRNAs and how they are regulated under chemo-radiotherapy. Hence, our overall goal is to decipher how protein HuR influences oral mucositis gene expression during chemo-radiotherapy. Second, oral mucositis initiates post-translational modification of HuR which in turn, promotes inflammation and apoptosis through mRNA stability. Interestingly, HuR undergoes cleavage modifications under chemotherapy; hence, we seek to understand whether HuR cleavage during chemotherapy is important in HuR association with mRNAs. Finally, we will test whether overexpression of HuR protect oral mucositis through repressing inflammation and apoptosis through mRNA turnover pathway. Thus, our data will provide a foundation for understanding the role of HuR in oral mucositis-associated gene regulation and will be pivotal for future studies into HuR-associated oral diseases.

描述（由申请人提供）：我们提出的研究将确定通过RNA结合蛋白（RBP）改变口腔粘膜炎发育和进展的转录后调节，这些调节是大多数真核细胞中基因表达的关键调节剂。这些蛋白会影响mRNA代谢的关键方面，包括核转移和细胞质出口，运输，储存，翻译和周转率。首先，在各种RNA结合蛋白中，HUR是一种影响细胞对应激的反应，增生性的突出蛋白信号，免疫触发器和发育提示。 HUR编码许多炎症和凋亡相关的mRNA，包括细胞因子，白介素和促凋亡因子，这些因素是我们打算研究的下游靶标。鉴于Hur对这些关键调节剂的表达的影响，我们对Hur蛋白结合mRNA以及在化学降射疗法下如何调节它们很感兴趣。因此，我们的总体目标是破译蛋白质HUR如何影响化学疗法期间的口腔粘膜炎基因表达。其次，口腔粘膜炎引发了对HUR的翻译后修饰，这反过来又通过mRNA稳定性促进了炎症和凋亡。有趣的是，HUR在化学疗法下进行了切割修饰。因此，我们试图了解化学疗法期间的HUR分裂在与mRNA的关联中是否重要。最后，我们将测试HUR的过表达是否通过通过mRNA转换途径抑制炎症和凋亡来保护口腔粘膜炎。因此，我们的数据将为理解HUR在与口服粘膜炎相关的基因调控中的作用提供基础，并将对与HUR相关的口腔疾病进行研究至关重要。