Selective cytotoxicity of recombinant STXA1-GM-CSF protein in hematopoetic cancer cells
Chimeric proteins are composed of a cell-targeting moiety and a cell-killing moiety. In this study, a chimeric protein, STXA1-GM-CSF, composed of catalytic domain of Shiga toxin (A1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) was constructed and expressed in E. coli. Cytotoxicity, receptor blocking, and neutralization experiments revealed that the chimeric protein induced cytotoxic effect on different cell lines. This effect was found to be specific, due to the presence of the killing moiety (A1), which exerts its effect through a specific GM-CSF-targeting domain, by binding to its receptor present on those cell lines. These initial investigations indicate that the chimeric protein was functional; further analyses are required for its application.
Keywordsshiga-toxin hGM-CSF cancer cytotoxicity chimeric protein
acute myeloid leukemia
(human) granulocyte-macrophage colony-stimulating factor
sodium docecyl sulfate–polyacrylamide gel electrophoresis
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