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

• Published in: Biochimica et biophysica acta 2011-07, Vol.1809 (7), p.285-294
• Main Authors: Hew, Hoi Chin, Liu, Hanshao, Lu, Zheng-Guang, Kimura, Junko, Miki, Yoshio, Yoshida, Kiyotsugu
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - physiology; Cell Line, Tumor; DNA damage; DNA Damage - physiology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Evi-1; Humans; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; MDS1 and EVI1 Complex Locus Protein; PKCδ; PLZF; Promyelocytic Leukemia Zinc Finger Protein; Protein Kinase C-delta - genetics; Protein Kinase C-delta - metabolism; Proto-Oncogenes - genetics; Signal Transduction - physiology; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - physiology
• ISSN: 1874-9399; 0006-3002; 1876-4320
• DOI: 10.1016/j.bbagrm.2011.02.004

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. [Display omitted] ► 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.