Identification of Evi-1 as a novel effector of PKCδ in the apoptotic response to DNA damage

Protein kinase C delta (PKCδ), a PKC family isoform, regulates diverse signal transduction pathways during DNA damage to induce apoptosis. To explore the apoptosis mechanism that PKCδ modulates, we sought to uncover transcription factor targets of PKCδ by devising a screening strategy that utilizes ChIP-cloning and microarray analysis. Transcription factor candidates were generated with the application of public access data-mining tools and this resulted in the identification of Evi-1 as a novel PKCδ-mediated DNA damage responsive molecule. The results demonstrated that PKCδ is constitutively associated with Evi-1. PKCδ regulated Evi-1 to activate PLZF transcription upon genotoxic stress. Furthermore, both Evi-1 and PLZF were associated with DNA damage-stimulated apoptosis. Taken together, we have discovered a novel regulation of Evi-1, which transactivates PLZF, by PKCδ to induce cell death in response to genotoxic stress.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (94 K)Download as PowerPoint slideResearch highlights► PKCδ induces apoptosis in response to DNA damage. ► PKCδ regulates Evi-1 to activate PLZF transcription. ► Evi-1 is associated with DNA damage-stimulated cell death.