人鸟氨酸脱羧酶基因的克

发布时间：2018-05-13 06:15

本文选题：鸟氨酸脱羧酶 + 多胺　；参考：《山东大学》2005年博士论文

【摘要】：鸟氨酸脱羧酶(Ornithine decarboxylase, ODC)(EC 4.1.1.17)是多胺代谢过程中的第一个限速酶。多胺广泛存在于真核生物细胞中,含有多个碱性的氨基,能与核酸分子相互结合,并促进DNA的生物合成,RNA的转录以及蛋白质的翻译,起到稳定细胞结构、增强核酸和蛋白质的合成的作用,为细胞的增殖提供物质基础从而促进细胞的增殖。凡生长旺盛的组织,如胚胎、再生肝等组织,细胞中多胺的含量均较高。高特异性的多胺合成抑制剂可以干扰非洲爪蟾卵母细胞的激素诱导的ODC活性,随后抑制其减数分裂及排卵。多胺的代谢与肿瘤的发生也有着密切的关系。早期的研究发现,病毒诱导原代成纤维细胞转化时,腐胺和精脒的含量增多。多胺在维持肿瘤细胞恶性表型中也起重要作用,抑制多胺合成可抑制肿瘤细胞增殖并诱导其分化及凋亡,引起肿瘤恶性表型逆转。由于多胺为ODC的产物,因此ODC对细胞的正常发育及异常增殖也起重要作用。 ODC及多胺水平升高几乎是所有种类的癌细胞的特征。用强力的肿瘤促进剂刺激上皮细胞后的早期变化之一就是ODC活性迅速、显著、一过性的诱导升高。ODC的合成受多种因素的影响,激素、生长因子、肿瘤刺激因子、病毒以及癌基因均能诱导ODC的合成,从而使细胞内的多胺水平增加。ODC基因表达可在转录、mRNA的降解、mRNA的翻译、酶蛋白的降解几个水平上进行调控。ODC基因被认为是一个立早基因,其中包含的应答元件可与几种反式作用因子结合,包括cAMP应答元件,胰岛素应答元件及几个Sp1结合位点等。ODC基因的诱导还对多种原癌基因的信号传导具有重要作用,如ras,v-src和myc基因被激活后对细胞的转化过程中常伴随着ODC基因的表达和多胺含量的增加。正常细胞中生长因子对ODC的调节是快速而短暂的,而肿瘤刺激因子、病毒及癌基因对ODC的作用是持续的。这些事实表明细胞内的ODC过度表达伎多胺生物合成增多,可能是细胞过度增殖,最终导致肿瘤发生的重要原因之一。
[Abstract]:Ornithine decarboxylase (ODC)(EC 4.1.1.17) is the first rate-limiting enzyme in polyamine metabolism. Polyamines are widely found in eukaryotic cells, containing many basic amino groups, which can bind to nucleic acid molecules, promote the transcription of DNA biosynthesis and protein translation, and stabilize the cellular structure. Enhance the synthesis of nucleic acid and protein, provide a material basis for cell proliferation and promote cell proliferation. The content of polyamines in the cells is higher in the tissues with high growth, such as embryo, regenerated liver and so on. High specific polyamine synthesis inhibitors can interfere with hormone-induced ODC activity of Xenopus laevis oocytes and then inhibit meiosis and ovulation of Xenopus laevis oocytes. The metabolism of polyamines is also closely related to tumorigenesis. Early studies showed that the contents of putrescine and spermidine increased when the virus induced the transformation of primary fibroblasts. Polyamines also play an important role in maintaining malignant phenotypes of tumor cells. Inhibition of polyamine synthesis can inhibit proliferation, induce differentiation and apoptosis of tumor cells, and induce reversal of malignant phenotypes of tumor cells. As polyamines are products of ODC, ODC also plays an important role in the normal development and abnormal proliferation of cells. Increased levels of ODC and polyamines are characteristic of almost all types of cancer cells. One of the early changes after stimulation of epithelial cells with strong tumor promoters is that the activity of ODC is rapid, significant and transient. The synthesis of ODC is affected by many factors, such as hormones, growth factors, tumor stimulating factors. Both virus and oncogene can induce the synthesis of ODC, which can increase the level of polyamines in cells. ODC gene expression can be regulated at several levels of transcriptional mRNAs degradation and enzymatic protein degradation. ODC gene is considered to be an early gene. The induction of ODC gene including cAMP response element, insulin response element and several Sp1 binding sites can also play an important role in signal transduction of many proto-oncogenes. For example, the expression of ODC gene and the increase of polyamine content are often associated with the activation of rashniv-src and myc genes. The regulation of ODC by growth factor in normal cells is rapid and transient, while the effect of tumor stimulating factor, virus and oncogene on ODC is continuous. These facts suggest that the increase of ODC overexpression in cells may be one of the important reasons for the over-proliferation of cells and ultimately the tumorigenesis.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R346

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