Activation of c-Jun N-terminal kinase antagonizes an anti-apoptotic action of Bcl-2.
Bcl-2 is an intracellular membrane-associated protein that prevents cell death induced by a variety of apoptotic stimuli. A mechanism by which Bcl-2 exerts an anti-cell death effect is, however, not fully understood. In the present study, Bcl-2 suppressed cell death of N18TG neuroglioma cells caused by various apoptotic stresses, including etoposide, staurosporine, anisomycin, and ultraviolet irradiation. Concomitantly, Bcl-2 disrupted a signaling cascade to the c-Jun N-terminal kinase activation induced by the apoptotic stresses. Bcl-2 also prevented the etoposide-induced stimulation of MEKK1. Furthermore, overexpression of c-Jun N-terminal kinase antagonized the death-protective function of Bcl-2. These data suggest that suppression of the c-Jun N-terminal kinase signaling pathway may be critical for Bcl-2 action.
Park
J
J
Cell Biology Laboratory, Hanhyo Institute of Technology, 461-6, Jeonmin-dong, Yuseong-ku, Taejon 305-390, Korea.
Kim
I
I
Oh
Y J
YJ
Lee
K
K
Han
P L
PL
Choi
E J
EJ
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000494:pharmacology*; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D000841:Anisomycin; D005047:Etoposide; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019311:Staurosporine