First Author | Shih NY | Year | 1996 |
Journal | J Biol Chem | Volume | 271 |
Issue | 27 | Pages | 16040-6 |
PubMed ID | 8663197 | Mgi Jnum | J:33812 |
Mgi Id | MGI:81305 | Doi | 10.1074/jbc.271.27.16040 |
Citation | Shih NY, et al. (1996) Protein kinase C-delta mRNA is down-regulated transcriptionally and post-transcriptionally by 12-O-tetradecanoylphorbol-13-acetate. J Biol Chem 271(27):16040-6 |
abstractText | Activation of protein kinase C-delta (PKC-delta) by 12-O-tetradecanoylphorbol-13-acetate (TPA) is followed by a gradual decrease in detectable protein 12-24 h later in the mouse B lymphoma cell line A20. Down-regulation is associated with TPA-induced proteolysis and a 50-86% decrease in PKC-delta mRNA 0.5-24 h post-treatment which is due to both a 50% decrease in transcription and accelerated degradation of PKC-delta mRNA as determined using the pulse-chase method. Destabilization of PKC-delta mRNA is also observed when actinomycin D is added to cells pretreated with TPA for 2 h; however, addition of actinomycin D or cycloheximide prior to TPA treatment blocks destabilization. Addition of PKC inhibitors to TPA-treated cells also blocks destabilization of PKC-delta mRNA. Cells treated with TPA for 4 h contain an activity not found in control cells which destabilizes PKC-delta mRNA but not glyceraldehyde-3-phosphate dehydrogenase mRNA in vitro. Addition of TPA to control extracts fails to increase degradation of PKC-delta mRNA in vitro, suggesting that treatment of intact cells is required to induce the synthesis of a factor(s) that destabilizes PKC-delta mRNA. This factor(s) then acts along with transcriptional and post-translational regulatory mechanisms to down-regulate PKC-delta. |