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

摘要

Protein kinase C delta (PKCdelta), a PKC family isoform, regulates diverse signal transduction pathways during DNA damage to induce apoptosis. To explore the apoptosis mechanism that PKCdelta modulates, we sought to uncover transcription factor targets of PKCdelta 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 PKCdelta-mediated DNA damage responsive molecule. The results demonstrated that PKCdelta is constitutively associated with Evi-1. PKCdelta 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 PKCdelta to induce cell death in response to genotoxic stress.