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Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
DAPK2 is a novel E2F1/KLF6 target gene involved in their proapoptotic function
A Britschgi1, E Trinh, M Rizzi
11Experimental Oncology/Hematology, Department of Clinical Research, University of Bern, Bern, Switzerland.
Oncogene
|June 4, 2008
Summary
Death-associated protein kinase 2 (DAPK2) is activated by transcription factors E2F1 and KLF6, which are Sp1-dependent. This regulation plays a role in programmed cell death.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Death-associated protein kinase 2 (DAPK2) is a serine/threonine kinase involved in apoptosis.
- DAPK2 enhances granulocytic differentiation.
- Identifying transcriptional regulators of DAPK2 is crucial for understanding its role in cellular processes.
Purpose of the Study:
- To identify transcriptional regulators of the DAPK2 gene.
- To elucidate the mechanism by which E2F1 and Krüppel-like factor 6 (KLF6) regulate DAPK2 expression.
- To investigate the role of Sp1 transcription factor in DAPK2 regulation.
Main Methods:
- Cloning and analysis of the 5'-flanking region of the DAPK2 gene.
- Reporter assays to assess promoter activity.
- Site-directed mutagenesis and Sp1/KLF6-deficient cell lines to determine binding site importance.
- Chromatin immunoprecipitation (ChIP) to confirm in vivo binding.
- Knockdown and overexpression studies in cancer cell lines.
Main Results:
- E2F1 and KLF6 strongly activate the DAPK2 promoter.
- The activating elements are located in a GC-rich region containing binding sites for KLF6 and Sp1.
- Transcriptional activation of DAPK2 by E2F1 and KLF6 is dependent on Sp1.
- Sp1, E2F1, and KLF6 are recruited to the DAPK2 promoter in vivo.
- E2F1 and KLF6 cooperate to activate the DAPK2 promoter.
- DAPK2 upregulation by E2F1 or KLF6 leads to increased cell death, which is reduced upon DAPK2 inhibition.
Conclusions:
- DAPK2 is a novel Sp1-dependent target gene for E2F1 and KLF6.
- E2F1 and KLF6 regulate DAPK2 expression through Sp1.
- DAPK2 plays a significant role in E2F1- and KLF6-mediated cell death.
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