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

Byung Wook Min, Gun Kim Chang, Je Sang Ko, Yoongho Lim, Han Lee Young, Young Shin Soon

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)686-708
Number of pages23
JournalExperimental and Molecular Medicine
Volume40
Issue number6
DOIs
Publication statusPublished - 2008 Dec 31

Fingerprint

Transcription
Antineoplastic Agents
Doxorubicin
Protein Kinase C
Genes
Gene expression
Chemical activation
Lymphoid Leukemia
Gene Expression
Leukemia L1210
Luciferases
Point Mutation
Assays
Binding Sites
Apoptosis

Keywords

  • Activating transcription factor 2
  • Apoptosis
  • Doxorubicin
  • JNK mitogen-activated protein kinases
  • Protein kinase C-δ
  • Proto-oncogene proteins c-jun

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

Cite this

Transcription of the protein kinase C-δ gene is activated by JNK through c-Jun and ATF2 in response to the anticancer agent doxorubicin. / Min, Byung Wook; Chang, Gun Kim; Ko, Je Sang; Lim, Yoongho; Young, Han Lee; Soon, Young Shin.

In: Experimental and Molecular Medicine, Vol. 40, No. 6, 31.12.2008, p. 686-708.

Research output: Contribution to journalArticle

@article{82ca97d76ba542a99fd21d3134ba7a1d,
title = "Transcription of the protein kinase C-δ gene is activated by JNK through c-Jun and ATF2 in response to the anticancer agent doxorubicin",
abstract = "Expression of protein kinase C-δ (PKCδ) is up-regulated by apoptosis-inducing stimuli. However, very little is known about the signaling pathways that control PKCδ gene transcription. In the present study, we demonstrate that JNK stimulates PKCδ 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 PKCδ 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 PKCδ promoter. Our results suggest an additional role for a JNK signaling cascade in DXR-induced PKCδ gene expression.",
keywords = "Activating transcription factor 2, Apoptosis, Doxorubicin, JNK mitogen-activated protein kinases, Protein kinase C-δ, Proto-oncogene proteins c-jun",
author = "Min, {Byung Wook} and Chang, {Gun Kim} and Ko, {Je Sang} and Yoongho Lim and Young, {Han Lee} and Soon, {Young Shin}",
year = "2008",
month = "12",
day = "31",
doi = "10.3858/emm.2008.40.6.686",
language = "English",
volume = "40",
pages = "686--708",
journal = "Experimental and Molecular Medicine",
issn = "1226-3613",
publisher = "Korean Society of Med. Biochemistry and Mol. Biology",
number = "6",

}

TY - JOUR

T1 - Transcription of the protein kinase C-δ gene is activated by JNK through c-Jun and ATF2 in response to the anticancer agent doxorubicin

AU - Min, Byung Wook

AU - Chang, Gun Kim

AU - Ko, Je Sang

AU - Lim, Yoongho

AU - Young, Han Lee

AU - Soon, Young Shin

PY - 2008/12/31

Y1 - 2008/12/31

N2 - Expression of protein kinase C-δ (PKCδ) is up-regulated by apoptosis-inducing stimuli. However, very little is known about the signaling pathways that control PKCδ gene transcription. In the present study, we demonstrate that JNK stimulates PKCδ 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 PKCδ 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 PKCδ promoter. Our results suggest an additional role for a JNK signaling cascade in DXR-induced PKCδ gene expression.

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

KW - Activating transcription factor 2

KW - Apoptosis

KW - Doxorubicin

KW - JNK mitogen-activated protein kinases

KW - Protein kinase C-δ

KW - Proto-oncogene proteins c-jun

UR - http://www.scopus.com/inward/record.url?scp=61849127776&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61849127776&partnerID=8YFLogxK

U2 - 10.3858/emm.2008.40.6.686

DO - 10.3858/emm.2008.40.6.686

M3 - Article

VL - 40

SP - 686

EP - 708

JO - Experimental and Molecular Medicine

JF - Experimental and Molecular Medicine

SN - 1226-3613

IS - 6

ER -