Transcriptional and post-transcriptional regulation of the PKC delta gene by etoposide in L1210 murine leukemia cells: implication of PKC delta autoregulation.
Protein kinase C delta (PKC delta) plays an important role in the regulation of apoptosis in response to diverse anticancer agents. PKC delta is cleaved irreversibly to a catalytically active fragment in response to apoptotic stimuli; however, little information is available about the regulation of PKC delta gene expression. In this study, we found that the amount of steady-state PKC delta mRNA and protein was increased by etoposide in mouse L1210 leukemia cells. The transcriptional rate of the PKC delta gene and the stability of PKC delta mRNA were increased by treatment with etoposide, resulting in the accumulation of PKC delta protein. Rottlerin inhibited etoposide-induced PKC delta gene expression significantly, while Go6976, LY294002 and PD98059 had no effect. Further, both stable and adenovirus-mediated expression of a dominant negative PKC delta(KR) abrogated etoposide-induced PKC delta expression. Etoposide-stimulated PKC delta transcription but not PKC delta mRNA stability was blocked completely by pretreatment with rottlerin. Our data reveal a novel mechanism whereby PKC delta gene is regulated at the transcriptional and post-transcriptional level in the L1210 leukemia cell line.
Shin
Soon Young
SY
Division of Molecular and Life Science, College of Science and Technology, Hanyang University, Ansan 426-791, South Korea.
Kim
Chang Gun
CG
Ko
Jesang
J
Min
Do Sik
DS
Chang
Jong-Soo
JS
Ohba
Motoi
M
Kuroki
Toshio
T
Choi
Young Bong
YB
Kim
Young-Ho
YH
Na
Doe Sun
DS
Kim
Jin Woo
JW
Lee
Young Han
YH
D000098:Acetophenones / Q000494:pharmacology; D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D015153:Blotting, Western; D002458:Cell Fractionation; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D007938:Leukemia / Q000235:genetics*; D051379:Mice; D008954:Models, Biological; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics*; D051745:Protein Kinase C-delta; D012333:RNA, Messenger / Q000187:drug effects; D014158:Transcription, Genetic; D015854:Up-Regulation
D000098:Acetophenones; D000970:Antineoplastic Agents; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D005047:Etoposide; C085746:rottlerin; C497259:Prkcd protein, mouse; D011493:Protein Kinase C; D051745:Protein Kinase C-delta