Impaired immunoproteasome assembly and immune responses in PA28-/- mice
Impaired immunoproteasome assembly and immune responses in PA28-/- mice
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DOI：
10.1126/science.286.5447.2162
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发表时间：
1999-12-10
期刊：
影响因子：
56.9
通讯作者：
Yang, Y
中科院分区：
文献类型：
--
作者：
Preckel, T;Fung-Leung, WP;Yang, Y
在体外，PA28结合并激活蛋白酶体。结果表明，PA28b基因突变的小鼠缺乏PA28a和PA28b多肽，说明PA28在体内是一种异源低聚物。PA28(-/-)小鼠对来自外源性或内源性抗原的抗原表位的处理发生改变。在缺乏PA28的小鼠中，细胞毒性T淋巴细胞反应受损，免疫蛋白酶体的组装受到极大抑制。这些结果表明，PA28是免疫蛋白酶体组装所必需的，也是有效处理抗原所必需的，从而证明了PA28介导的蛋白酶体功能在免疫应答中的重要性。
In vitro PA28 binds and activates proteasomes. It is shown here that mice with a disrupted PA28b gene Lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered in PA28(-/-) mice. Cytotoxic T Lymphocyte responses are impaired, and assembly of immunoproteasomes is greatly inhibited in mice lacking PA28. These results show that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-mediated proteasome function in immune responses.