Abstract 273: Protein kinase C-iota self regulates its expression by regulating the activity of the transcription factor Elk-1

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Abstract Protein kinase C-iota (PKC-ι), a member of the atypical PKC family of Ser/Thr kinases has been recognized as an oncogene. PKC-ι manifests its effect by targeting various aspects of cancer cells such as growth, invasion and survival. Bcr-Abl has been shown to regulate the activation of the transcription factor ELK-1 which in turn regulates the expression of PKC-ι. Alternatively, we hypothesize that PKC-ι self regulates its expression by directly regulating the activity of ELK-1. Our preliminary data from immunoprecipitation studies show that PKC-ι directly associates with Elk-1 in neuroblastoma and glioma cells. PKC-ι directly phosphorylated cytoplasmic Elk-1 at Ser 383 in these cells. It has been reported that phosphorylation of cytoplasmic Elk-1 at Ser 383 results in conformational change that promotes the nuclear translocation of Elk-1, increased DNA binding and upregulation of its transcriptional activity. Furthermore, our data from cell cycle analysis showed that the nuclear translocation of Elk-1 coincided with the phosphorylation of cytoplasmic Elk-1 by PKC-ι. Robust phosphorylation of cytoplasmic Elk-1 was observed in the G1/S cell cycle phases, however, as the cells entered the M-phase, no phosphorylation of ELK-1 was observed. Similarly, the cytoplasmic to nuclear ratio of Elk-1 decreased as the cells entered the M-phase suggesting the role of PKC-ι in the promoting the nuclear translocation of Elk-1. Thus, our data supports our hypothesis that PKC-ι self regulates its expression by regulating the transcriptional activity of Elk-1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 273. doi:10.1158/1538-7445.AM2011-273