La autoantigen translocates to cytoplasm after cleavage during granzyme B-mediated cytotoxicity
La autoantigen translocates to cytoplasm after cleavage during granzyme B-mediated cytotoxicity
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DOI：
10.1016/j.lfs.2007.09.017
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发表时间：
2007-10-27
期刊：
影响因子：
6.1
通讯作者：
Eguchi, Katsumi
中科院分区：
文献类型：
--
作者：
Huang, Mingguo;Ida, Hiroaki;Eguchi, Katsumi
我们最近的报告表明，抗颗粒酶B诱导的SS-B（La）切割片段的自身抗体在原发性干燥综合征患者的血清中发现。本研究的目的是通过颗粒酶B诱导的细胞凋亡过程中La自身抗原的细胞内再分布来确定。我们开发了绿色荧光蛋白（GFP）-La和GFP-La Delta 220（产生颗粒酶B特异性切割La蛋白）融合蛋白。GFP-La蛋白定位于细胞核中，而GFP-La Delta 220蛋白主要存在于转化的A293 T细胞的细胞质中。富含颗粒酶B的YT细胞孵育后，核内GFP-La蛋白转位至胞浆。在YT细胞共培养后，人唾液腺大HSG细胞中的La蛋白被切割并从细胞核易位到细胞质。这些结果表明，La蛋白被颗粒酶B切割和N-末端La片段（27 kD）易位到细胞质中，从而导致一种新的自身抗体产生过程中颗粒酶B介导的细胞毒性。(c)2007年爱思唯尔公司All rights reserved.
Our recent report demonstrated that apoptosis-specific autoantibodies against granzyme B-induced cleavage fragments of SS-B (La) were found in the sera from patients with primary Sjogren's syndrome. The objective of this study was identified by the intracellular redistribution of La autoantigen during granzyme B-induced apoptosis. We developed green fluorescence protein (GFP)-La and GFP-La Delta 220 (generation of granzyme B-specific cleavage of La protein) fusion proteins. GFP-La protein was localized in the nucleus, whereas the GFP-La Delta 220 protein predominantly existed in the cytoplasm in transformed A293T cells. Nuclear GFP-La protein was translocated to cytoplasm after granzyme B enriched YT cells incubation. La protein in human salivary grand HSG cells is cleaved and translocated from the nucleus to the cytoplasm after YT cell co-cultivation. These results suggest that La protein is cleaved by granzyme B and N-terminal La fragment (27 kD) translocated to the cytoplasm, thus leading to a novel autoantibody production during granzyme B-mediated cytotoxicity. (c) 2007 Elsevier Inc. All rights reserved.