Abstract |
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.
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Authors | Byong Wook Min, Chang Gun Kim, Jesang Ko, Yoongho Lim, Young Han Lee, Soon Young Shin |
Journal | Experimental & molecular medicine
(Exp Mol Med)
Vol. 40
Issue 6
Pg. 699-708
(Dec 31 2008)
ISSN: 1226-3613 [Print] United States |
PMID | 19116455
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Activating Transcription Factor 2
- Anthracenes
- Antibiotics, Antineoplastic
- Proto-Oncogene Proteins c-jun
- pyrazolanthrone
- Doxorubicin
- Protein Kinase C-delta
- Mitogen-Activated Protein Kinase 8
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Topics |
- Activating Transcription Factor 2
(physiology)
- Animals
- Anthracenes
(pharmacology)
- Antibiotics, Antineoplastic
(pharmacology)
- Apoptosis
- Cell Line, Tumor
- Doxorubicin
(pharmacology)
- Mice
- Mitogen-Activated Protein Kinase 8
(physiology)
- Mutation
- Promoter Regions, Genetic
- Protein Kinase C-delta
(genetics, metabolism)
- Proto-Oncogene Proteins c-jun
(antagonists & inhibitors, physiology)
- Signal Transduction
(physiology)
- Transcription, Genetic
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