ASK-1 (apoptosis signal-regulating kinase 1) is a direct E2F target gene

The Biochemical Journal
Zoulika KherroucheDidier Monté

Abstract

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 apopto...Continue Reading

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Citations

Mar 11, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Larissa ArningJörg T Epplen
Sep 22, 2007·Annual Review of Pharmacology and Toxicology·Kohsuke TakedaHidenori Ichijo
Jul 12, 2008·Biochemical and Biophysical Research Communications·Hiromichi NaruyamaMakoto Nakanishi
Aug 3, 2010·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·David Engelmann, Brigitte M Pützer
May 10, 2007·Journal of Cellular and Molecular Medicine·B M Pützer
Sep 5, 2013·American Journal of Physiology. Endocrinology and Metabolism·Yulia HaimAssaf Rudich
Apr 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Wantae KimYingzi Yang
Feb 4, 2010·Molecular Cancer Research : MCR·Elaine Y C HsiaHong-Wu Chen

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