Molecular mechanisms involved in CD43-mediated apoptosis of TF-1 cells. Roles of transcription Daxx expression, and adhesion molecules.
CD43 (leukosialin, sialophorin), an abundant leukocyte surface sialoglycoprotein, regulates leukocyte adhesion and transmits activating signals in T cells and dendritic cells. Immobilized anti-CD43 monoclonal antibody (mAb) MEM-59 has been previously shown to induce apoptosis of hematopoietic progenitors. In this study we show that it also triggers apoptosis of the myeloid ... progenitor-derived cell line TF-1. The kinetics of the MEM-59-induced apoptosis were unusually slow, with the first apoptotic cells appearing 36-48 h after their contact with the immobilized antibody; in 5 days, 90% of the cells were dead. CD43-mediated apoptosis was enhanced by coimmobilized anti-CD45 mAb and partly suppressed by coimmobilized anti-CD50 (ICAM-3) or anti-CD99 mAb. The MEM-59-triggered apoptosis of TF-1 cells was also inhibited by the overexpression of an apoptotic regulator, Daxx. CD43-mediated apoptosis was preceded by the repression of the DNA binding activity of the transcription factor AP-1. DNA array screening revealed that the expression of several genes encoding apoptosis-regulating proteins, including 14-3-3 proteins and the granulocyte macrophage colony-stimulating factor (GM-CSF) receptor beta-subunit, was repressed in TF-1 cells bound to immobilized MEM-59. The down-regulation of 14-3-3 proteins and GM-CSF receptor beta was accompanied by translocation of the proapoptotic protein Bad to the mitochondria. These results suggest that engagement of CD43 may, presumably through the repressing transcription, initiate a Bad-dependent apoptotic pathway.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Antibodies, Monoclonal, Antigens, CD, Antigens, CD43, Antigens, CD45, Antigens, Differentiation, Apoptosis, Blotting, Western, Carrier Proteins, Cell Adhesion, Cell Adhesion Molecules, Cell Division, Cell Line, Cell Nucleus, Cross-Linking Reagents, DNA, Complementary, Down-Regulation, Electrophoresis, Polyacrylamide Gel, Flow Cytometry, Hematopoietic Stem Cells, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Kinetics, NF-kappa B, Nuclear Proteins, Oligonucleotides, Plasmids, Protein Binding, Protein Transport, Reverse Transcriptase Polymerase Chain Reaction, Sialoglycoproteins, Tetrazolium Salts, Thiazoles, Time Factors, Transcription, Genetic, Two-Hybrid System Techniques
Adaptor Proteins, Signal Transducing, Antibodies, Monoclonal, Antigens, CD, Antigens, CD43, Antigens, CD45, Antigens, Differentiation, Apoptosis, Blotting, Western, Carrier Proteins, Cell Adhesion, Cell Adhesion Molecules, Cell Division, Cell Line, Cell Nucleus, Cross-Linking Reagents, DNA, Complementary, Down-Regulation, Electrophoresis, Polyacrylamide Gel, Flow Cytometry, Hematopoietic Stem Cells, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Kinetics, NF-kappa B, Nuclear Proteins, Oligonucleotides, Plasmids, Protein Binding, Protein Transport, Reverse Transcriptase Polymerase Chain Reaction, Sialoglycoproteins, Tetrazolium Salts, Thiazoles, Time Factors, Transcription, Genetic, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Mar. 08, 2002
PubMed ID: 11773067
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