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Implication of the ERK Pathway on the Post-transcriptional Regulation of VEGF mRNA Stability

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MAP Kinase Signaling Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 661))

Abstract

Vascular Endothelial Growth Factor-A (VEGF-A) is one of the most important regulators of physiological and pathological angiogenesis. Constitutive activation of the ERK pathway and over-expression of VEGF-A are common denominators of tumours of different origins. Understanding VEGF-A regulation is of primary importance to better comprehend pathological angiogenesis. VEGF-A expression is regulated at all steps of its synthesis including transcription, mRNA stability, an under estimated way of VEGF regulation and translation. In this chapter, we present the link between VEGF mRNA stability through AU-rich sequences present in its 3′-untranslated region (3′-UTR) and the ERK pathway. We present several methods that have been used to demonstrate that ERKs increase VEGF mRNA half-life. This mRNA-stabilising effect is partly due to reduction of the mRNA destabilising effects of Tristetraprolin (TTP), an AU-Rich binding protein which binds to VEGF-A mRNA 3′-UTR.

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Acknowledgements

This work was supported by the French association for cancer research (ARC, 4932), by the Association for International Cancer Research (AICR) and the French National Institute of Cancer (INCa).

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Authors and Affiliations

  1. Biochemistry and Experimental Pathology Unit, Pasteur Institute of Tunis, Tunis, Tunisia

    Khadija Essafi-Benkhadir

  2. Institute of Developmental Biology and Cancer Research UMR CNRS, University of Nice Sophia Antipolis, UMR CNRS 6543, Nice, France

    Jacques Pouysségur

  3. Institute of Developmental Biology and Cancer Research UMR, University of Nice Sophia Antipolis, UMR CNRS 6543, Nice, France

    Gilles Pagès

Authors
  1. Khadija Essafi-Benkhadir
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  2. Jacques Pouysségur
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  3. Gilles Pagès
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Correspondence to Gilles Pagès .

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Editors and Affiliations

  1. Dept. Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

    Rony Seger

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Essafi-Benkhadir, K., Pouysségur, J., Pagès, G. (2010). Implication of the ERK Pathway on the Post-transcriptional Regulation of VEGF mRNA Stability. In: Seger, R. (eds) MAP Kinase Signaling Protocols. Methods in Molecular Biology, vol 661. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-795-2_28

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  • DOI: https://doi.org/10.1007/978-1-60761-795-2_28

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-794-5

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