Nature Communications (Apr 2020)
Interference with ERK-dimerization at the nucleocytosolic interface targets pathological ERK1/2 signaling without cardiotoxic side-effects
- Angela Tomasovic,
- Theresa Brand,
- Constanze Schanbacher,
- Sofia Kramer,
- Martin W. Hümmert,
- Patricio Godoy,
- Wolfgang Schmidt-Heck,
- Peter Nordbeck,
- Jonas Ludwig,
- Susanne Homann,
- Armin Wiegering,
- Timur Shaykhutdinov,
- Christoph Kratz,
- Ruth Knüchel,
- Hans-Konrad Müller-Hermelink,
- Andreas Rosenwald,
- Norbert Frey,
- Jutta Eichler,
- Dobromir Dobrev,
- Ali El-Armouche,
- Jan G. Hengstler,
- Oliver J. Müller,
- Karsten Hinrichs,
- Friederike Cuello,
- Alma Zernecke,
- Kristina Lorenz
Affiliations
- Angela Tomasovic
- Institute of Pharmacology and Toxicology, University of Würzburg
- Theresa Brand
- Institute of Pharmacology and Toxicology, University of Würzburg
- Constanze Schanbacher
- Institute of Pharmacology and Toxicology, University of Würzburg
- Sofia Kramer
- Institute of Pharmacology and Toxicology, University of Würzburg
- Martin W. Hümmert
- Institute of Pharmacology and Toxicology, University of Würzburg
- Patricio Godoy
- IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund
- Wolfgang Schmidt-Heck
- Leibniz Institute for Natural Product Research and Infection Biology -Hans Knoell Institute-
- Peter Nordbeck
- Comprehensive Heart Failure Center
- Jonas Ludwig
- Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg
- Susanne Homann
- Institute of Pharmacology and Toxicology, University of Würzburg
- Armin Wiegering
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg
- Timur Shaykhutdinov
- Leibniz-Institut für Analytische Wissenschaften − ISAS−e.V.
- Christoph Kratz
- Leibniz-Institut für Analytische Wissenschaften − ISAS−e.V.
- Ruth Knüchel
- Institute of Pathology, University Hospital Aachen, RWTH Aachen
- Hans-Konrad Müller-Hermelink
- Institute of Pathology, University of Würzburg
- Andreas Rosenwald
- Institute of Pathology, University of Würzburg
- Norbert Frey
- Department of Internal Medicine III, University of Kiel
- Jutta Eichler
- Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg
- Dobromir Dobrev
- Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen
- Ali El-Armouche
- Department of Pharmacology and Toxicology, TU Dresden
- Jan G. Hengstler
- IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund
- Oliver J. Müller
- Department of Internal Medicine III, University of Kiel
- Karsten Hinrichs
- Leibniz-Institut für Analytische Wissenschaften − ISAS−e.V.
- Friederike Cuello
- Institute of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf
- Alma Zernecke
- Institute of Experimental Biomedicine, University Hospital Würzburg, University of Würzburg
- Kristina Lorenz
- Institute of Pharmacology and Toxicology, University of Würzburg
- DOI
- https://doi.org/10.1038/s41467-020-15505-4
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 16
Abstract
Drugs targeting dysregulated ERK1/2 signaling can cause severe cardiac side effects, precluding their wide therapeutic application. Here, a new and cardio-safe targeting strategy is presented that interferes with ERK dimerization to prevent pathological ERK1/2 signaling in the heart and cancer.
