Transcription of the protein kinase C-delta gene is activated by JNK through c-Jun and ATF2 in response to the anticancer agent doxorubicin.
Expression of protein kinase C-delta (PKCdelta) is up-regulated by apoptosis-inducing stimuli. However, very little is known about the signaling pathways that control PKCdelta gene transcription. In the present study, we demonstrate that JNK stimulates PKCdelta gene expression via c-Jun and ATF2 in response to the anticancer agent doxorubicin (DXR) in mouse lymphocytic leukemia L1210 cells. Luciferase reporter assays showed that DXR-induced activation of the PKCdelta promoter was enhanced by ectopic expression of JNK1, c-Jun, or ATF2, whereas it was strongly reduced by expression of dominant negative JNK1 or by treatment with the JNK inhibitor SP600125. Furthermore, point mutations in the core sequence of the c-Jun/ATF2 binding site suppressed DXR-induced activation of the PKCdelta promoter. Our results suggest an additional role for a JNK signaling cascade in DXR-induced PKCdelta gene expression.
Min
Byong Wook
BW
Department of Surgery, Korea University College of Medicine, Ansan 425-707, Korea.
Kim
Chang Gun
CG
Ko
Jesang
J
Lim
Yoongho
Y
Lee
Young Han
YH
Shin
Soon Young
SY
D051698:Activating Transcription Factor 2 / Q000502:physiology*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000502:physiology*; D009154:Mutation; D011401:Promoter Regions, Genetic; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic
D051698:Activating Transcription Factor 2; D000873:Anthracenes; D000903:Antibiotics, Antineoplastic; D016755:Proto-Oncogene Proteins c-jun; C432165:pyrazolanthrone; D004317:Doxorubicin; D051745:Protein Kinase C-delta; D048055:Mitogen-Activated Protein Kinase 8