Transcriptional and post-transcriptional regulation of the PKC delta gene by etoposide in L1210 murine leukemia cells: implication of PKC delta autoregulation

Journal of Molecular Biology
Soon Young ShinYoung Han Lee

Abstract

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.

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Citations

Jul 8, 2008·Leukemia & Lymphoma·Amanda J Redig, Leonidas C Platanias
Jan 2, 2007·Biochemical and Biophysical Research Communications·Soon Young ShinYoung Han Lee
May 19, 2006·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Soon Young ShinYoung Han Lee
Jun 5, 2008·Journal of Cellular Biochemistry·Orit BossiTamar Tennenbaum
May 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ricky CheungRonald G Collman

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