PI31 is a modulator of proteasome formation and antigen processing
PI31 is a modulator of proteasome formation and antigen processing
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PI31 是蛋白酶体形成和抗原加工的调节剂
DOI：
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发表时间：
2002
影响因子：
11.1
通讯作者：
A. Sijts
中科院分区：
文献类型：
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作者：
D. Zaiss;S. Standera;P. Kloetzel;A. Sijts
蛋白酶体系统负责产生大多数MHC I类结合肽，其调节通过20 S蛋白酶体与几种调节蛋白的相互作用发生。其中之一是PI 31，其在体外作为蛋白酶体活性的抑制剂。在这里，我们证明，而不是抑制蛋白酶体功能，PI 31作为一个选择性的调制器的蛋白酶体介导的步骤，在MHC I类抗原加工。PI 31在小鼠胚胎细胞中的过表达对蛋白酶体介导的蛋白水解没有影响。相反，PI 31，它定位于核膜/内质网膜，选择性地干扰免疫蛋白酶体前体复合物的成熟。因此，PI 31的过表达消除了免疫蛋白酶体依赖性细胞毒性T淋巴细胞表位的MHC I类呈递，并降低了IFN-γ处理的小鼠胚胎细胞上的表面MHC I类水平。因此，PI 31代表蛋白酶体形成和蛋白酶体介导的抗原加工的细胞调节剂。
Regulation of the proteasome system, which is responsible for the generation of most MHC class I-bound peptides, occurs through the interaction of the 20S proteasome with several regulatory proteins. One of these is PI31, which acts in vitro as an inhibitor of proteasome activity. Here, we demonstrate that, rather than inhibiting proteasome function, PI31 acts as a selective modulator of the proteasome-mediated steps in MHC class I antigen processing. Overexpression of PI31 in mouse embryonic cells has no impact on proteasome-mediated proteolysis. Instead, PI31, which localizes at the nuclear envelope/endoplasmic reticulum membrane, selectively interferes with the maturation of immunoproteasome precursor complexes. Consequently, overexpression of PI31 abrogates MHC class I presentation of an immunoproteasome-dependent cytotoxic T lymphocyte epitope and reduces the surface MHC class I levels on IFN-γ-treated mouse embryonic cells. Thus, PI31 represents a cellular regulator of proteasome formation and of proteasome-mediated antigen processing.