Exp Mol Med.  2008 Dec;40(6):699-708. 10.3858/emm.2008.40.6.699.

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

• Min BW
• Kim CG
• Ko J
• Lim Y
• Lee YH
• Shin SY

• KMID: 1072950
• DOI: http://doi.org/10.3858/emm.2008.40.6.699

Abstract

Expression of protein kinase C-delta (PKC delta) is up-regulated by apoptosis-inducing stimuli. However, very little is known about the signaling pathways that control PKC delta gene transcription. In the present study, we demonstrate that JNK stimulates PKC delta 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 PKC delta 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 PKC delta promoter. Our results suggest an additional role for a JNK signaling cascade in DXR-induced PKC delta gene expression.

Keyword

activating transcription factor 2; apoptosis; doxorubicin; JNK mitogen-activated protein kinases; protein kinase C-delta; proto-oncogene proteins c-jun

MeSH Terms

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