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Cell-penetrating autoantibody induces caspase-mediated apoptosis through catalytic hydrolysis of DNA.

Authors
Lee, EJ; Jang, EJ; Lee, E; Yu, J; Chung, HY; Jang, YJ
Citation
Bioorganic & medicinal chemistry, 15(5):2016-2023, 2007
Journal Title
Bioorganic & medicinal chemistry
ISSN
0968-08961464-3391
Abstract
In the present study, we investigated the substrate specificity of catalytic activity of a cytotoxic anti-DNA monoclonal autoantibody, G1-5, which was obtained from an MRL-lpr/lpr mouse by hybridoma technology. The antibody catalyzed hydrolysis of single- and double-stranded DNA with a higher substrate specificity for thymine than adenine by either beta-glycosidic or phosphodiester bond cleavage. The hydrolysis rate (kcat) showed maximum at acidic pH conditions, suggesting that the catalytic site of the antibody contains essential carboxylic group(s). Treatment of cells with the antibody promoted cell death and induced the activation of caspases. The cell death induced by the antibody was inhibited by the pan-caspase inhibitor. Furthermore, the antibody binds to cell membrane and penetrates into the cells. Our results suggest that the cell death is initiated by antibodies penetrating to cells and nucleus, hydrolyzing considerable amount of DNA, and mediating the caspase-dependent apoptotic pathway.
MeSH terms
Amino Acid SequenceAutoantibodies/chemistryAutoantibodies/metabolism*Caspases/metabolism*CatalysisDNA/metabolism*HL-60 CellsHumansHydrolysisMolecular Sequence DataSequence Homology, Amino Acid
DOI
10.1016/j.bmc.2006.12.037
PMID
17234421
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
장, 영주
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