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

M Huang, H Ida, K Arima, H Nakamura, T Aramaki… - Life sciences, 2007 - Elsevier
M Huang, H Ida, K Arima, H Nakamura, T Aramaki, K Fujikawa, M Tamai, M Kamachi…
Life sciences, 2007Elsevier
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 …
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.
Elsevier