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...

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Veröffentlicht in:Biochimica et biophysica acta 2011-07, Vol.1809 (7), p.285-294
Hauptverfasser: Hew, Hoi Chin, Liu, Hanshao, Lu, Zheng-Guang, Kimura, Junko, Miki, Yoshio, Yoshida, Kiyotsugu
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container_end_page 294
container_issue 7
container_start_page 285
container_title Biochimica et biophysica acta
container_volume 1809
creator Hew, Hoi Chin
Liu, Hanshao
Lu, Zheng-Guang
Kimura, Junko
Miki, Yoshio
Yoshida, Kiyotsugu
description 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.
doi_str_mv 10.1016/j.bbagrm.2011.02.004
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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
title Identification of Evi-1 as a novel effector of PKCδ in the apoptotic response to DNA damage
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