Role of p170 in lung tumorigenesis

p170 在肺肿瘤发生中的作用

• 批准号: 6807020
• 负责人: Jian-Ting Zhang
• 金额: $ 30.14万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6807020
• 关键词: athymic mouse; carcinogenesis; cell growth regulation; cell line; glycoproteins; luciferin monooxygenase; lung neoplasms; messenger RNA; neoplastic growth; posttranslational modifications; protein degradation; protein quantitation /detection; ribonucleotide reductase; transcription factor; translation factor

DESCRIPTION (provided by applicant): Gene expression can be regulated at both the transcriptional and translational level. Most of the translational regulation occurs at the level of translation initiation. Unlike transcription factors, eukaryotic translation Initiation Factors (eIF) have not been well recognized for their role in controlling cell growth. Recent studies suggest that elF4E, eIF2, and the p48 subunit of eIF3 may be involved in cell-growth control and oncogenesis. More recently, the expression of the putative subunit p170 of eIF3 was found to be up regulated in human lung, breast, cervical, and esophageal cancers. We have observed that p170 may be an important regulator for the expression of ribonucleotide reductase M2. Thus, eIF3 p170 may be an important regulator for controlling the expression of cell growth regulatory proteins and, thus, cell growth. The long-term goal of this project is to establish the role of eIF3 p170 in cell growth control and its relationship to human cancer. The hypothesis to be tested is that p170 is a major player in regulating the synthesis of specific cell growth control proteins. To this end, we plan to accomplish the following specific aims within the funding period: (1) to determine whether over-expression of pl70 causes tumorigenesis; (2) to determine whether p 170 regulates cell growth by controlling the synthesis of DNA synthesis enzymes such as ribonucleotide reductase M2; and (3) to study the regulation of eIF3 p170 expression. The role of a putative housekeeping protein, p170, in tumorigenesis has not been suggested previously and thus this study is novel. The information and probes obtained from this study will help us understand the molecular mechanism of translational control of cell growth. This work will certainly add to our understanding of the functional mechanism of translation initiation of protein synthesis.

描述（由申请人提供）：基因表达可以在转录和翻译级别进行调节。大多数翻译调节发生在翻译启动级别。与转录因子不同，真核翻译起始因子（EIF）在控制细胞生长中的作用尚未得到很好的认可。最近的研究表明，ELF4E，EIF2和EIF3的p48亚基可能参与细胞生长的控制和肿瘤发生。最近，发现EIF3的假定亚基P170的表达在人肺，乳房，宫颈和食管癌中受到调节。我们已经观察到P170可能是表达核糖核苷酸还原酶M2的重要调节剂。因此，EIF3 p170可能是控制细胞生长调节蛋白表达以及细胞生长的重要调节剂。该项目的长期目标是确定EIF3 P170在细胞生长控制及其与人类癌症的关系中的作用。要检验的假设是P170是调节特定细胞生长控制蛋白的合成的主要参与者。为此，我们计划在资金期内完成以下特定目标：（1）确定PL70的过表达是否会导致肿瘤发生； （2）确定P 170是否通过控制DNA合成酶（例如核糖核苷酸还原酶M2）的合成来调节细胞生长； （3）研究EIF3 P170表达的调节。以前尚未提出假定的管家蛋白P170在肿瘤发生中的作用，因此这项研究是新颖的。从这项研究中获得的信息和探针将有助于我们了解细胞生长转化控制的分子机制。这项工作肯定会增加我们对蛋白质合成的翻译起始功能机理的理解。