Immunogenetics of the proteasome

蛋白酶体是负责产生由MHC I类分子结合的肽的多亚基蛋白酶。在这项研究中，我们试图深入了解IFN-γ调节的蛋白酶体亚基的结构，功能和起源。1）IFN-γ诱导的20 S蛋白酶体亚基的起源：MHC染色体复制模型的提出三个IFN-γ诱导的20 S蛋白酶体亚基被认为是由组成型表达的20 S蛋白酶体亚基通过基因复制而产生的。我们的工作表明，它们不是通过三个独立的复制出现的，而是通过涉及MHC区域的块复制出现的，并且这种复制发生在脊椎动物进化的早期，最有可能发生在有颌脊椎动物的共同祖先中。2）IFN-γ调节的蛋白酶体亚单位基因的克隆和结构分析从129/SvJ小鼠中系统地克隆了IFN-γ调节的蛋白酶体亚单位基因，并对其染色体定位进行了测定。迄今为止表征的基因是：Psmb JO、Psmb 7、Psmb 5、Psmel、Psme 2和Psme 3。这些基因组克隆现在被用于构建基因敲除小鼠。

The proteasome is the multisubunit protease responsible for the production of peptides bound by MHC class I molecules. In this study, we attempted to gain insights into the structure, function, and origin of IFN-gamma regulated proteasome subunits. The results we obtained are as follows :1) Origin of IFN-gamma-inducible 20S proteasome subunits : Proposal of the chromosomal duplication model of the MHCThe three IFN-gamma-inducible 20S proteasome subunits are thought to have emerged by gene duplication from their constitutively expressed counterparts. Our work showed that they emerged not by three independent duplications but by block duplication involving the MHC region, and that this duplication took place early in vertebrate evolution, most likely in a common ancestor of jawed vertebrates. This series of work has led to the proposal of the chromosomal duplication model of the MHC.2) Cloning and structural analysis of the IFN-gamma-regulated proteasome subunit genesThe IFN-gamma-regulated proteasome subunit genes were cloned systematically from 129/SvJ mice and their chromosomal localization was determined. The genes thus far characterized are : Psmb JO, Psmb7, Psmb5, Psmel, Psme2, and Psme3. These genomic clones are now being used to construct knock-out mice.