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

Soon Young Shin, Chang Gun Kim, Jesang Ko, Do Sik Min, Jong Soo Chang, Motoi Ohba, Toshio Kuroki, Young Bong Choi, Young Ho Kim, Doe Sun Na, Jin Woo Kim, Young Han Lee

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Abstract

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

Original languageEnglish
Pages (from-to)681-693
Number of pages13
JournalJournal of Molecular Biology
Volume340
Issue number4
DOIs
Publication statusPublished - 2004 Jul 16

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All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Cite this

Shin, S. Y., Kim, C. G., Ko, J., Min, D. S., Chang, J. S., Ohba, M., Kuroki, T., Choi, Y. B., Kim, Y. H., Na, D. S., Kim, J. W., & Lee, Y. H. (2004). Transcriptional and post-transcriptional regulation of the PKCδ gene by etoposide in L1210 murine leukemia cells: Implication of PKCδ autoregulation. Journal of Molecular Biology, 340(4), 681-693. https://doi.org/10.1016/j.jmb.2004.04.006