In the present study, we show that E2Fs (E2 promoter-binding factors) regulate the expression of ASK-1 (apoptosis signal-regulating kinase 1), which encodes a mitogen-activated protein kinase kinase kinase, also known as MAP3K5. Its mRNA expression is cell-cycle-regulated in human T98G cells released from serum starvation. Moreover, overexpression and RNA interference experiments support the requirement of endogenous E2F/DP (E2F dimerization partner) activity for ASK-1 expression. Characterization of the human ASK-1 promoter demonstrates that the −95/+11 region is critical for E2F-mediated up-regulation. Chromatin immunoprecipitation assays show that E2F1–E2F4 are bound in vivo to the ASK-1 promoter in cycling cells, probably through a non-consensus E2F-binding site located 12 bp upstream of the transcription start site. Mutation of this site completely abolishes the ASK-1 promoter response to E2Fs as well as the E2F1 binding in electrophoretic mobility-shift experiments. Our results indicate that E2Fs modulate the expression of ASK-1 and suggest that some of the cellular functions of ASK-1 may be under the control of E2F transcription factors. Moreover, the up-regulation of ASK-1 may also favour the p53-independent E2F1 apoptotic activity.
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Research Article|
May 29 2006
ASK-1 (apoptosis signal-regulating kinase 1) is a direct E2F target gene
Zoulika Kherrouche;
Zoulika Kherrouche
*CNRS UMR 8161, Institut de Biologie de Lille, 1 rue Calmette, BP 447, 59021 Lille, France
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Alexandre Blais;
Alexandre Blais
†New York University School of Medicine, Department of Pathology, Room MSB 504, 550 First Avenue, New York, NY 10016, U.S.A.
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Elisabeth Ferreira;
Elisabeth Ferreira
*CNRS UMR 8161, Institut de Biologie de Lille, 1 rue Calmette, BP 447, 59021 Lille, France
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Yvan De Launoit;
Yvan De Launoit
*CNRS UMR 8161, Institut de Biologie de Lille, 1 rue Calmette, BP 447, 59021 Lille, France
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Didier Monté
Didier Monté
1
*CNRS UMR 8161, Institut de Biologie de Lille, 1 rue Calmette, BP 447, 59021 Lille, France
1To whom correspondence should be addressed (email didier.monte@ibl.fr).
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Publisher: Portland Press Ltd
Received:
December 14 2005
Revision Received:
February 27 2006
Accepted:
March 03 2006
Accepted Manuscript online:
March 03 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 396 (3): 547–556.
Article history
Received:
December 14 2005
Revision Received:
February 27 2006
Accepted:
March 03 2006
Accepted Manuscript online:
March 03 2006
Citation
Zoulika Kherrouche, Alexandre Blais, Elisabeth Ferreira, Yvan De Launoit, Didier Monté; ASK-1 (apoptosis signal-regulating kinase 1) is a direct E2F target gene. Biochem J 15 June 2006; 396 (3): 547–556. doi: https://doi.org/10.1042/BJ20051981
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