C-Jun modulates apoptosis but not terminal cell differentiation in murine erythroleukemia cells.
The proto-oncogene c-Jun has been implicated in the control of cell proliferation and differentiation and more recently in the regulation of apoptosis. We have previously reported the involvement of c-Jun in the erythroid differentiation block in murine erythroleukemia (MEL) cells. As reported here, we investigated the role of c-Jun in the regulation of terminal differentiation and apoptosis of MEL cells by studying different stable transfectant clones containing c-jun constructs in sense or antisense orientation. c-Jun did not prevent cell growth arrest in G0/G1 and p21 induction that are normally associated with terminal differentiation induced by DMSO treatment, suggesting that c-Jun may uncouple phenotypic differentiation and terminal cell division in the MEL cell system. Spontaneous apoptosis was accelerated in c-jun expressing MEL cells before and after DMSO treatment. Moreover, c-Jun sensitized apoptosis induced by various drugs. Drug-induced apoptosis was associated with c-Jun N-terminal kinase (JNK) activation and c-Jun N-terminal phosphorylation (JNP). In contrast, overexpression of c-jun delayed apoptosis in serum-starved cells, indicating that c-Jun may reduce or accelerate apoptosis in MEL cells depending on the nature of the apoptotic stimulus. These results suggest that the proto-oncogene c-Jun may modulate differentiation and apoptosis of leukemic cells.
Poindessous-Jazat
V
V
INSERM U268, Hôpital Paul Brousse, 14 avenue Paul Vaillant Couturier, 94807 Villejuif, France.
Augery-Bourget
Y
Y
Robert-Lézénès
J
J
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D016373:DNA, Antisense / Q000235:genetics; D003630:Daunorubicin / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D016758:Genes, jun; D048031:JNK Mitogen-Activated Protein Kinases; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D059005:Topoisomerase II Inhibitors; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; C493957:Cdkn1a protein, mouse; D016895:Culture Media, Serum-Free; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016373:DNA, Antisense; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D011500:Protein Synthesis Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D059005:Topoisomerase II Inhibitors; D000841:Anisomycin; D005047:Etoposide; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D004121:Dimethyl Sulfoxide; D003630:Daunorubicin