Signaling through the antigen receptor of B lymphocytes activates a p53-independent pathway of c-Myc-induced apoptosis.
Deregulated expression of c-Myc has been shown to induce or enhance apoptosis in various different cell types. c-Myc requires p53 for apoptosis in some but not all the cell types, indicating heterogeneous mechanisms for c-Myc-induced apoptosis. In B lymphoma line WEHI-231, stable expression of c-Myc has been demonstrated to protect cells from BCR-mediated apoptosis. However, stable expression of c-Myc carrying pro-apoptotic functions may generate variant cells resistant to apoptosis. By utilizing an inducible system for c-Myc, we demonstrated here that deregulated expression of c-Myc induced apoptosis of WEHI-231 by itself, indicating that c-Myc induces apoptosis in WEHI-231 as is the case for other cell types. When transactivation of p53 was inactivated, WEHI-231 cells overexpressing c-Myc no longer underwent apoptosis in the absence of other stimuli, but showed markedly enhanced apoptosis in the presence of BCR ligation. These results indicate that deregulated c-Myc expression enhances apoptosis by a p53-independent pathway in the presence of BCR signaling but requires p53 for apoptosis in the absence of BCR crosslinking in WEHI-231. BCR ligation may thus activate a p53-independent pathway of c-Myc-induced apoptosis.
Hagiyama
H
H
Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Adachi
T
T
Yoshida
T
T
Nomura
T
T
Miyasaka
N
N
Honjo
T
T
Tsubata
T
T
D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D004958:Estradiol