| Research Abstract |
The proteasome is the multi-subunit 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-γ regulated proteasome subunits. The results we obtained are as follows :
1) Origin of IFN-γ-inducible 20S proteasome subunits : Proposal of the chromosomal duplication model of the MHC
The three IFN-γ-inducible 20S proteasome subunits are thought to have emerged by gene duplication from their constitutively expressed counterparts. We showed that these subunit genes emerged by two rounds of block duplication involving the MHC region thought to have taken 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) Structural and functional analysis of the IFN-γ-regulated proteasome subunit genes
We cloned the following IFN-γ-regulated proteasome subunit genes from 129/SvJ mice : Psmb10, Psmb7, Psmb5, Psme1, Psme2, and Psme3, and produced Psme1/Psme2 double knock-out mice as well as mice deficient in the Psme3 gene. Analysis of these mice demonstrated that PA28α/β encoded by Psme1/Psme2 is essential for processing of certain antigens, whereas PA28γ encoded by Psme3 is unlikely to be involved in antigen presentation by MHC class I molecules.
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