Transcriptional and post-transcriptional regulation of the PKCδ gene by etoposide in L1210 murine leukemia cells:: Implication of PKCδ autoregulation

Protein kinase Cdelta (PKCdelta) plays an important role in the regulation of apoptosis in response to diverse anticancer agents. PKCdelta is cleaved irreversibly to a catalytically active fragment in response to apoptotic stimuli; however, little information is available about the regulation of PKCdelta gene expression. In this study, we found that the amount of steady-state PKCdelta mRNA and protein was increased by etoposide in mouse L1210 leukemia cells. The transcriptional rate of the PKCdelta gene and the stability of PKCdelta mRNA were increased by treatment with etoposide, resulting in the accumulation of PKCdelta protein. Rottlerin inhibited etoposide-induced PKCdelta gene expression significantly, while Go6976, LY294002 and PD98059 had no effect. Further, both stable and adenovirus-mediated expression of a dominant negative PKCdelta(KR) abrogated etoposide-induced PKCdelta expression. Etoposide-stimulated PKCdelta transcription but not PKCdelta mRNA stability was blocked completely by pretreatment with rottlerin. Our data reveal a novel mechanism whereby PKCdelta gene is regulated at the transcriptional and post-transcriptional level in the L1210 leukemia cell line. (C) 2004 Elsevier Ltd. All rights reserved.