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.
Bibliographical noteFunding Information:
We thank Dr Sung Ho Ryu (Pohang University of Science and Technology, Korea) for helpful discussion and comments, and Dr Jang-Soo Chun (Kwangju Institute of Science and Technology, Korea) for providing the plasmids pMTH/PKCδ and pMTH/PKCδ(KR). This work was supported by Grant R01-2002-00000167-0 from the Basic Research Program of the Korea Science and Engineering Foundation.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology