| Research Abstract |
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 MHC
The 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 genes
The 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.
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