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Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase

Author

Listed:
  • Virginia Guarani

    (Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University)

  • Gianluca Deflorian

    (IFOM, the FIRC Institute of Molecular Oncology, IFOM-IEO Campus)

  • Claudio A. Franco

    (Vascular Biology Laboratory, London Research Institute – Cancer Research UK)

  • Marcus Krüger

    (Max Planck Institute for Heart and Lung Research)

  • Li-Kun Phng

    (Vascular Biology Laboratory, London Research Institute – Cancer Research UK
    Present address: Cell Biology and Biophysics, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.)

  • Katie Bentley

    (Vascular Biology Laboratory, London Research Institute – Cancer Research UK)

  • Louise Toussaint

    (Laboratory of Protein Signaling and Interactions, GxABT, B-5030 Gembloux and Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liege)

  • Franck Dequiedt

    (Laboratory of Protein Signaling and Interactions, GxABT, B-5030 Gembloux and Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liege)

  • Raul Mostoslavsky

    (Massachusetts General Hospital Cancer Center, Harvard Medical School)

  • Mirko H. H. Schmidt

    (Molecular Signal Transduction, Institute of Neurology (Edinger Institute), Goethe University)

  • Barbara Zimmermann

    (Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University)

  • Ralf P. Brandes

    (Vascular Research Centre, Institute for Cardiovascular Physiology, Goethe University)

  • Marina Mione

    (IFOM, the FIRC Institute of Molecular Oncology, IFOM-IEO Campus)

  • Christoph H. Westphal

    (Sirtris, a GSK Company)

  • Thomas Braun

    (Max Planck Institute for Heart and Lung Research)

  • Andreas M. Zeiher

    (Internal Medicine III, Goethe University)

  • Holger Gerhardt

    (Vascular Biology Laboratory, London Research Institute – Cancer Research UK
    Consultant Group Leader, Vascular Patterning Laboratory, Vesalius Research Center, VIB, Campus Gasthuisberg)

  • Stefanie Dimmeler

    (Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University)

  • Michael Potente

    (Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University
    Internal Medicine III, Goethe University)

Abstract

Notch signalling in angiogenesis Notch signalling coordinates angiogenesis by controlling the specification of endothelial cells into tip cells that lead the way in growing blood vessels and the stalk cells that follow. Michael Potente and colleagues have identified a previously unknown component in Notch signalling regulation in endothelial cells that may provide a mechanism for fine-tuning angiogenesis in response to metabolic requirements and angiogenic stress. They show that the metabolism- and redox-sensing deacetylase SIRT1 deacetylates the Notch1 intracellular domain directly, thereby controlling its stability and turnover and negatively modulating Notch signalling. Inactivation of SIRT1 impairs angiogenesis in zebrafish and mice.

Suggested Citation

  • Virginia Guarani & Gianluca Deflorian & Claudio A. Franco & Marcus Krüger & Li-Kun Phng & Katie Bentley & Louise Toussaint & Franck Dequiedt & Raul Mostoslavsky & Mirko H. H. Schmidt & Barbara Zimmerm, 2011. "Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase," Nature, Nature, vol. 473(7346), pages 234-238, May.
    • Handle: RePEc:nat:nature:v:473:y:2011:i:7346:d:10.1038_nature09917
    DOI: 10.1038/nature09917
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