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Structure and Cell Biology of a Novel Multicatalytic Proteinase Complex

新型多催化蛋白酶复合物的结构和细胞生物学

基本信息

批准号：
01304029
负责人：
ICHIHARA Akira
金额：
$ 7.04万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

Multicatalytic proteinase complex (Proteasomes) is a large assembly of many protein components with various protease activities. In 1990 we carried out a co-operative research to investigate structure and functions of proteasomes.1. Structural analysis --- cDNAs of 15 components of the proteasomes from yeast, rat and human were cloned and sequenced. These sequences showed no homology with any known proteins indicating that the proteasomes consist of subunits which are new protein family. This consideration is supported by the facts that homology among subunits from different animals was very high. Assembly of subunits to form a ring-shape particle can be observed by electron microscopy and similarity of shape among proteasomes of different animals suggests that structure of complex is important for the function.2. Functions of proteasomes --- It was shown that proteasomes play important role in embryogenesis, particularly maturation and fertilization of egg. The expression of proteasome mRNA was very high in cancerous tissues of liver, kidney and blood cells. It was also found that proteasomes translocate etween cytosol and nucleus during cell growth. These results indicate that proteasomes relate closely with cell growth and differentiation. This notion was supported by experiments of gene disruption of yeast subunits. Yeast received disrupted genes became lethal.

多催化蛋白酶复合物（蛋白酶体）是许多具有不同蛋白酶活性的蛋白质组分的大型集合体。1990年我们进行了一项合作研究，以研究蛋白酶体的结构和功能。结构分析-对酵母、大鼠和人的蛋白酶体的15个组分的cDNA进行了克隆和测序。这些序列与已知蛋白质序列没有同源性，表明该蛋白酶体由新的蛋白质亚基组成。不同动物的亚基之间的同源性非常高，这一事实支持了这一考虑。电镜下可以观察到亚基组装成环状颗粒，不同动物蛋白酶体之间的形状相似性表明复合物的结构对功能有重要影响.蛋白酶体的功能--研究表明蛋白酶体在胚胎发生中发挥重要作用，特别是卵子的成熟和受精。蛋白酶体mRNA在肝、肾、血细胞癌组织中表达较高。在细胞生长过程中，蛋白酶体在细胞质和细胞核之间发生了转位。这些结果表明，蛋白酶体与细胞的生长和分化密切相关。这一观点得到了酵母亚基基因破坏实验的支持。接受了被破坏的基因的酵母变得致命。