title: Ultraviolet-induced junD activation and apoptosis in myeloblastic leukemia ML-1 cells.
abstract: The exposure of mammalian cells to UV irradiation induces the expression of immediate early genes such as c-jun and c-fos and activates the transcription factors AP-1 and NF-kappaB. JunD is one of the three members of the Jun family and shares some functional characteristics with c-Jun. In the present study, we found that the exposure of myeloblastic leukemia ML-1 cells to UV light (UVC) caused a significant increase in junD mRNA expression within 5 min that persisted for a period of 3 h. The activation of protein kinase C (PKC) with 12-O-tetradecaoylphorbol-13-acetate (TPA) also induced increases in junD expression similar to those of UV irradiation. In addition, UV irradiation- and TPA-induced increases in junD expression were completely abolished by GF-109203X, a PKC-specific inhibitor. UV irradiation activated intracellular signaling pathways including extracellular regulated kinase-2 (Erk-2), c-Jun N-terminal kinases-1 (JNK-1), and p38. However, TPA-induced activation of PKC affected only Erk-2 activity, and GF-109203X (a PKC inhibitor) markedly suppressed UV-induced Erk-2 activation. To further investigate the effect of UV-induced Erk-2 activation on the expression of junD mRNA, cDNA encoding mitogen-activated protein kinase kinase (MEK1) was overexpressed in ML-1 cells. The overexpression of MEK1 enhanced substantially junD expression in response to UV or TPA. In contrast, the suppression of Erk activation with PD98059, a specific inhibitor of MEK1, inhibited UV- and TPA-induced junD mRNA expression, UV-induced increases in caspase-3 activities, and cell death. In addition, the overexpression of junD enhanced the UV irradiation-induced increases in caspase-3 activity and cell death. We conclude that UV irradiation-induced increases in junD expression in ML-1 cells are mediated through activation of the PKC-coupled Erk-2 signaling pathway and play an important role in ML-1 cell apoptosis.
authors.affiliation: Division of Molecular Medicine, Harbor-UCLA Medical Center, School of Medicine, University of California Los Angeles, Torrance, California 90502, USA.
authors.forename: Tie
authors.initials: T
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Luo
authors.initials: L
authors.lastname: Lu
mesh_terms: D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D013755:Tetradecanoylphorbol Acetate