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Papers In Press, published online ahead of print December 31, 2001
J. Biol. Chem, 10.1074/jbc.M108048200
Submitted on August 21, 2001
Revised on December 31, 2001
Accepted on December 31, 2001

Molecular mechanisms involved in CD43-mediated apoptosis of TF-1 cells: Roles of transcription, Daxx expression and adhesion molecules

Lukáš Cermák, Šárka ;Šímová, Alexandros Pintzas, Václav Horejší, and Ladislav Andera

Dept. of Leukocyte Antigens, Institute of Molecular Genetics, Prague 4 CZ 14220

Corresponding Author: andera{at}biomed.cas.cz

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, as the first apoptotic cells appeared 36-48 hrs after their contact with the immobilized antibody; in 5 days, 90% of the cells were dead. The CD43-mediated apoptosis was enhanced by co-immobilized anti-CD45 mAb and partly suppressed by co-immobilized anti-CD50 (ICAM-3) or anti-CD99 mAbs. The MEM-59-triggered apoptosis of TF-1 cells was also inhibited by the overexpression of an apoptotic regulator, Daxx. The 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 GM-CSF receptor beta-subunit, was repressed in TF-1 cells bound to immobilized MEM-59. The downregulation of 14-3-3 proteins and GM-CSF R beta was accompanied by the translocation of the pro-apoptotic protein Bad to the mitochondria. These results suggest that engagement of CD43 may, presumably through the repressing transcription, initiate a Bad-dependent apoptotic pathway.


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