...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >IFN-γ-induced immune adaptation of the proteasome system is an accelerated and transient response
【24h】

IFN-γ-induced immune adaptation of the proteasome system is an accelerated and transient response

机译：IFN-γ诱导的蛋白酶体系统的免疫适应是加速和短暂的反应

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Peptide generation by the proteasome is rate-limiting in MHC class I-restricted antigen presentation in response to IFN-γ. IFN-γ-induced de novo formation of immunoproteasomes, therefore, essentially supports the rapid adjustment of the mammalian immune system. Here, we report that the molecular interplay between the proteasome maturation protein (POMP) and the pro-teasomal β5i subunit low molecular weight protein 7 (LMP7) has a key position in this immune adaptive program. IFN-γ-induced coincident biosynthesis of POMP and LMP7 and their direct interaction essentially accelerate immunoproteasome biogenesis compared with constitutive 20S proteasome assembly. The dynamics of this process is determined by rapid LMP7 activation and the immediate LMP7-dependent degradation of POMP. Silencing of POMP expression impairs recruitment of both β5 subunits into the proteasome complex, resulting in decreased proteasome activity, reduced MHC class I surface expression, and induction of apoptosis. Furthermore, our data reveal that immunoproteasomes exhibit a considerably shortened half-life, compared with constitutive pro-teasomes. In consequence, our studies demonstrate that the cyto-kine-induced rapid immune adaptation of the proteasome system is a tightly regulated and transient response allowing cells to return rapidly to a normal situation once immunoproteasome function is no longer required.
机译：蛋白酶体产生的肽在响应IFN-γ的MHC I类限制性抗原呈递中是限速的。因此，IFN-γ诱导的免疫蛋白酶体从头形成，基本上支持哺乳动物免疫系统的快速调节。在这里，我们报告蛋白酶体成熟蛋白（POMP）和蛋白酶体β5i亚基低分子量蛋白7（LMP7）之间的分子相互作用在此免疫适应程序中具有关键地位。与组成型20S蛋白酶体组装相比，IFN-γ诱导的POMP和LMP7的同时生物合成及其直接相互作用实质上加速了免疫蛋白酶体的生物发生。此过程的动力学取决于快速LMP7激活和POMP依赖于LMP7的立即降解。沉默POMP表达会削弱两个β5亚基向蛋白酶体复合物中的募集，从而导致蛋白酶体活性降低，MHC I类表面表达降低以及诱导细胞凋亡。此外，我们的数据显示，与组成型蛋白酶体相比，免疫蛋白酶体的半衰期大大缩短。因此，我们的研究表明，蛋白酶体系统的细胞因子诱导的快速免疫适应是严格调节的和短暂的反应，一旦不再需要免疫蛋白酶体功能，可使细胞迅速恢复正常状态。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号