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A molecular link between E2F-1 and the MAPK cascade
Journal article   Open access   Peer reviewed

A molecular link between E2F-1 and the MAPK cascade

Jianli Wang, Wen Hong Shen, Yan J Jin, Paul W Brandt-Rauf and Yuxin Yin
The Journal of biological chemistry, v 282(25), pp 18521-18531
22 Jun 2007
DOI: https://doi.org/10.1074/jbc.M610538200
PMID: 17452331
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
http://www.jbc.org/content/282/25/18521.full.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1074/jbc.M610538200View
Published, Version of Record (VoR) Open

Abstract

Animals Base Sequence Cell Line, Tumor Dual-Specificity Phosphatases E2F1 Transcription Factor - physiology Humans MAP Kinase Signaling System Mice Mice, Nude Mitogen-Activated Protein Kinase Phosphatases Molecular Sequence Data Oxidative Stress Promoter Regions, Genetic Protein Phosphatase 2 Protein Tyrosine Phosphatases - physiology Transcription, Genetic Transcriptional Activation
Transcription factor E2F-1 mediates apoptosis and suppresses tumorigenesis. The mechanisms by which E2F-1 functions in these processes are largely unclear. We report here that E2F-1 acts as a transcriptional regulator of MKP-2 (MAPK phosphatase-2), a dual specificity protein phosphatase (DUSP4) with stringent substrate specificity for MAPKs. We show that E2F-1 is required for the cellular apoptotic response to oxidative damage. MKP-2 is greatly increased following oxidative stress, and E2F-1 is necessary for that induction. We found that E2F-1 is physically associated with the MKP-2 promoter and can transactivate the promoter of the MKP-2 gene. Specifically, E2F-1 binds to a perfect palindromic motif in the MKP-2 promoter. Finally, we show that this E2F-1/MKP-2 pathway mediates apoptosis under oxidative stress and that MKP-2 suppresses tumor formation in nude mice. Our findings demonstrate that E2F-1 is a transcriptional activator of MKP-2 and that MKP-2 is an essential cell death mediator in the E2F-1 pathway. Characterization of MKP-2 as a cell death mediator may lead to the development of new strategies for cancer treatment.

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33 citations in Web of Science
33 citations in Scopus

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Web of Science research areas
Biochemistry & Molecular Biology
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