DAPK2 is a novel E2F1/KLF6 target gene involved in their proapoptotic function.

Détails

ID Serval
serval:BIB_3B30B1EB117E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
DAPK2 is a novel E2F1/KLF6 target gene involved in their proapoptotic function.
Périodique
Oncogene
Auteur⸱e⸱s
Britschgi A., Trinh E., Rizzi M., Jenal M., Ress A., Tobler A., Fey M.F., Helin K., Tschan M.P.
ISSN
1476-5594 (Electronic)
ISSN-L
0950-9232
Statut éditorial
Publié
Date de publication
25/09/2008
Peer-reviewed
Oui
Volume
27
Numéro
43
Pages
5706-5716
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Death-associated protein kinase 2 (DAPK2) belongs to a family of proapoptotic Ca(2+)/calmodulin-regulated serine/threonine kinases. We recently identified DAPK2 as an enhancing factor during granulocytic differentiation. To identify transcriptional DAPK2 regulators, we cloned 2.7 kb of the 5'-flanking region of the DAPK2 gene. We found that E2F1 and Krüppel-like factor 6 (KLF6) strongly activate the DAPK2 promoter. We mapped the E2F1 and KLF6 responsive elements to a GC-rich region 5' of exon 1 containing several binding sites for KLF6 and Sp1 but not for E2F. Moreover, we showed that transcriptional activation of DAPK2 by E2F1 and KLF6 is dependent on Sp1 using Sp1/KLF6-deficient insect cells, mithramycin A treatment to block Sp1-binding or Sp1 knockdown cells. Chromatin immunoprecipitation revealed recruitment of Sp1 and to lesser extent that of E2F1 and KLF6 to the DAPK2 promoter. Activation of E2F1 in osteosarcoma cells led to an increase of endogenous DAPK2 paralleled by cell death. Inhibition of DAPK2 expression resulted in significantly reduced cell death upon E2F1 activation. Similarly, KLF6 expression in H1299 cells increased DAPK2 levels accompanied by cell death that is markedly decreased upon DAPK2 knockdown. Moreover, E2F1 and KLF6 show cooperation in activating the DAPK2 promoter. In summary, our findings establish DAPK2 as a novel Sp1-dependent target gene for E2F1 and KLF6 in cell death response.
Mots-clé
Apoptosis, Apoptosis Regulatory Proteins/genetics, Apoptosis Regulatory Proteins/physiology, Binding Sites, Calcium-Calmodulin-Dependent Protein Kinases/genetics, Calcium-Calmodulin-Dependent Protein Kinases/physiology, Cells, Cultured, Death-Associated Protein Kinases, E2F1 Transcription Factor/physiology, Humans, Kruppel-Like Factor 6, Kruppel-Like Transcription Factors/physiology, Promoter Regions, Genetic, Proto-Oncogene Proteins/physiology, Sp1 Transcription Factor/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/03/2021 17:32
Dernière modification de la notice
13/03/2021 7:26
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