Transcription of the protein kinase C-delta gene is activated by JNK through c-Jun and ATF2 in response to the anticancer agent doxorubicin.
10.3858/emm.2008.40.6.699
- Author:
Byong Wook MIN
1
;
Chang Gun KIM
;
Jesang KO
;
Yoongho LIM
;
Young Han LEE
;
Soon Young SHIN
Author Information
1. Department of Surgery, Korea University College of Medicine, Ansan, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
activating transcription factor 2;
apoptosis;
doxorubicin;
JNK mitogen-activated protein kinases;
protein kinase C-delta;
proto-oncogene proteins c-jun
- MeSH:
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
- From:Experimental & Molecular Medicine
2008;40(6):699-708
- CountryRepublic of Korea
- Language:English
-
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.
