Analyses of Molecular Assembly and Diversity of Proteasomes

蛋白酶体是一种异常大的细胞装置，它选择性地降解必须从细胞中消除的不必要的蛋白质。我们通过一组蛋白酶体专属的分子伴侣的发现确定了蛋白酶体组装的分子机制，这些分子伴侣有助于蛋白酶体的正确形成。此外，我们还建立了蛋白酶体多样性的新概念。在此之前，我们发现了“免疫蛋白酶体”，它强调免疫反应中的特殊功能。最近，我们还发现了另一个独特的“胸腺蛋白酶体”，它只在胸腺中表达。我们发现胸腺蛋白酶体缺陷小鼠的胸腺发育存在CD8+T细胞的缺陷，提示胸腺蛋白酶体在胸腺阳性选择过程中MHC I类限制性CD8+T细胞谱系的发展中起关键作用。

The proteasome is an unusually large cellular apparatus that selectively degrades unnecessary proteins, which must be eliminated from the cells. We defined the molecular mechanisms underling proteasome assembly by the findings of a set of proteasome-dedicated molecular chaperones that assist the correct formation of the proteasome. In addition, we established the new concept on the diversity of the proteasome. Previously, we discovered the "immunoproteasome", which emphasized the specialized functions in immune responses. Lately, we also identified another unique "thymoproteasome", which is expressed exclusively in the thymus. We found that thymoproteasome-deficient mice displayed defective thymic development of CD8+T cells, suggesting a key role for thymoproteasome in the development of the MHC class I-restricted CD8+T cell repertoire during thymic positive selection.