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Transcription of the protein kinase C-delta gene is activated by JNK through c-Jun and ATF2 in response to the anticancer agent doxorubicin.

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.
AuthorsByong Wook Min, Chang Gun Kim, Jesang Ko, Yoongho Lim, Young Han Lee, Soon Young Shin
JournalExperimental & molecular medicine (Exp Mol Med) Vol. 40 Issue 6 Pg. 699-708 (Dec 31 2008) ISSN: 1226-3613 [Print] United States
PMID19116455 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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