La autoantigen translocates to cytoplasm after cleavage during granzyme B-mediated cytotoxicity

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• 作者：Mingguo Huang ; Hiroaki Ida ; Kazuhiko Arima ; Hideki Nakamura ; Toshiyuki Aramaki ; Keita Fujikawa ; Mami Tamai ; Makoto Kamachi ; Atsushi Kawakami ; Hironori Yamasaki ; Tomoki Origuchi ; Katsumi Eguchi
• 关键词：Granzyme B ; La (SS-B) ; Translocation ; Apoptosis
• 刊名：Life Sciences
• 出版年：2007
• 出版时间：27 October 2007
• 年：2007
• 卷：81
• 期：19-20
• 页码：1461-1466
• 全文大小：585 K

文摘

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 Sjögren'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-LaΔ220 (generation of granzyme B-specific cleavage of La protein) fusion proteins. GFP-La protein was localized in the nucleus, whereas the GFP-LaΔ220 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.