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

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 Zimmermann, Ralf P. Brandes, Marina Mione, Christoph H. Westphal, Thomas Braun, Andreas M. Zeiher, Holger Gerhardt, Stefanie Dimmeler and Michael Potente ()
Additional contact information
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
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
Stefanie Dimmeler: Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University
Michael Potente: Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University

Nature, 2011, vol. 473, issue 7346, 234-238

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.

Date: 2011
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DOI: 10.1038/nature09917

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