Activation of c-Jun N-terminal Kinase Antagonizes an Anti-apoptotic Action of Bcl-2

• Published in: The Journal of biological chemistry Vol. 272; no. 27; pp. 16725 - 16728
• Main Authors: Park, Jihyun, Kim, Injung, Oh, Young Jun, Lee, Ko-woon, Han, Pyung-Lim, Choi, Eui-Ju
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.07.1997; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Anisomycin - pharmacology; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Apoptosis - radiation effects; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Carcinogens - pharmacology; DNA Fragmentation; Enzyme Activation; Etoposide - pharmacology; JNK Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinases; Protein Synthesis Inhibitors - pharmacology; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - pharmacology; Staurosporine - pharmacology; Transfection; Tumor Cells, Cultured; Ultraviolet Rays
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.27.16725

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.