PROSTAGLANDIN SYNTHASE'S ROLE IN TRANSFORMATION BY V-SRC

前列腺素合成酶在 V-SRC 转化中的作用

• 批准号: 3200086
• 负责人: DANIEL L SIMMONS
• 金额: $ 10.36万
• 依托单位: BRIGHAM YOUNG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-03-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3200086
• 关键词: RNA splicing; Rous sarcoma virus; antiinflammatory agents; biological signal transduction; cell cycle; chick embryo; developmental genetics; dexamethasone; drug interactions; enzyme mechanism; fatty acid biosynthesis; fibroblasts; gel electrophoresis; genetic recombination; laboratory rabbit; messenger RNA; molecular cloning; monoclonal antibody; neoplastic transformation; posttranslational modifications; prostaglandin endoperoxide synthase; prostaglandins; thromboxanes; tissue /cell culture; viral carcinogenesis

The enzyme prostaglandin G/H synthase catalyzes the rate-limiting steps in the synthesis of prostaglandins, which are potent bioactive molecules involved with inflammation, pain, clotting, vasodilation and other important processes in the body. Nonsteroidal anti-inflammatory drugs exert many of their pharmacological effects by inhibiting this enzyme. Heretofore, only one prostaglandin G/H synthase has been known, but our laboratory has recently discovered a new form which is induced in chicken embryo fibroblasts by v-src, the oncogene of Rous sarcoma virus. The synthesis of this form is tightly linked to mitogenesis in fibroblasts in culture, suggesting that it plays a role in cell division. The goal of the proposed studies is to characterize this new form of prostaglandin synthesis, with particular attention being given to its function in v-src-induced neoplasia. Immunological and enzymatic studies will compare the mitogen-inducible synthase with the non- mitogen-inducible form with regard to enzyme activities, subcellular localization, posttranslational modification, developmental- and tissue- specific expression, structure of cellular membranes, interaction with non-steroidal anti-inflammatory drugs, and expression during normal cell division and during tumorigenesis. The molecular mechanism(s) by which the mitogen-induced form of prostaglandin synthase is regulated during cell division will also be placed on a unique posttranscriptional mechanism which appears to decrease translation of the protein in non- dividing cells by inhibiting the splicing of a 5' intron that interrupts the coding sequence of the MRNA.

酶前列腺素G/H合酶催化速率限制步骤 在合成前列腺素的合成中，这是有效的生物活性分子 涉及炎症，疼痛，凝结，血管舒张和其他 体内的重要过程。非甾体类抗炎药 通过抑制这种酶发挥许多药理作用。 迄今 实验室最近发现了一种新形式 鸡胚胎成纤维细胞由V-SRC，Rous肉瘤病毒的癌基因。 这种形式的合成与有丝分裂的合成紧密相关 培养中的成纤维细胞，表明它在细胞中起作用 分配。拟议研究的目的是表征这一新的 前列腺素合成的形式，特别注意 它在V-SRC诱导的肿瘤中的功能。免疫学和酶促 研究将比较有丝分裂原诱导的合酶与非 - 关于酶活性，亚细胞的促丝原诱导形式 定位，翻译后修饰，发育和组织 - 特定表达，细胞膜的结构，与 非甾体抗炎药和正常细胞期间的表达 分裂和肿瘤发生期间。分子机制 在 细胞分裂也将放置在独特的转录后 似乎减少了蛋白质翻译的机制 通过抑制中断的5'内含子的剪接来划分细胞 mRNA的编码顺序。