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

Life Sci. 2007 Oct 27;81(19-20):1461-6. doi: 10.1016/j.lfs.2007.09.017. Epub 2007 Oct 2.

Abstract

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-LaDelta220 (generation of granzyme B-specific cleavage of La protein) fusion proteins. GFP-La protein was localized in the nucleus, whereas the GFP-LaDelta220 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Blotting, Western
  • Cell Line
  • Cell Survival
  • Cells, Cultured
  • Cytoplasm / metabolism*
  • Granzymes / metabolism*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Microscopy, Confocal
  • Protein Transport
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • SS-B Antigen
  • Transfection

Substances

  • Autoantigens
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • Green Fluorescent Proteins
  • Granzymes