title: Identification of Evi-1 as a novel effector of PKCδ in the apoptotic response to DNA damage.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Medical Research Institute Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hoi Chin
authors.initials: HC
authors.lastname: Hew
authors.forename: Hanshao
authors.initials: H
authors.lastname: Liu
authors.forename: Zheng-Guang
authors.initials: ZG
authors.lastname: Lu
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
authors.forename: Kiyotsugu
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D000074008:MDS1 and EVI1 Complex Locus Protein; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D011519:Proto-Oncogenes / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014157:Transcription Factors; C092037:ZBTB16 protein, human; D051745:Protein Kinase C-delta