Subunit specific inhibitors of proteasomes and their potential for immunomodulation.
Subunit specific inhibitors of proteasomes and their potential for immunomodulation.
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DOI：
10.1016/j.cbpa.2014.08.012
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发表时间：
2014-12
影响因子：
7.8
通讯作者：
Groettrup M
中科院分区：
文献类型：
--
作者：
Kisselev AF;Groettrup M
免疫系统中组成型20S蛋白酶体的专门变体，如免疫蛋白酶体和胸腺蛋白酶体，含有活性位点承载亚基，其在切割优先级和底物结合口袋方面不同。免疫蛋白酶体在抗原加工和参与自身免疫发病机制的促炎性T辅助细胞的分化中起着至关重要的作用。免疫蛋白酶体和组成型蛋白酶体的选择性抑制剂最近已经产生，其干扰自身免疫性疾病的发展和进展。在这里，我们描述了这些抑制剂和它们的治疗潜力，从临床前模型预测。
Specialized variants of the constitutive 20S proteasome in the immune system like the immunoproteasomes and the thymoproteasome contain active site-bearing subunits which differ in their cleavage priorities and substrate binding pockets. The immunoproteasome plays a crucial role in antigen processing and for the differentiation of pro-inflammatory T helper cells which are involved in the pathogenesis of autoimmunity. Selective inhibitors of the immunoproteasome and constitutive proteasome have recently been generated which interfere with the development and progression of autoimmune diseases. Here we describe these inhibitors and their therapeutic potential as predicted from preclinical models.