Dimethyl fumarate is an allosteric covalent inhibitor of the p90 ribosomal S6 kinases

Jacob Lauwring Andersen; Borbala Gesser; Erik Daa Funder; Christine Juul Fælled Nielsen; Helle Gotfred-Rasmussen; Mads Kirchheiner Rasmussen; Rachel Toth; Kurt Vesterager Gothelf; J. Simon C. Arthur; Lars Iversen; Poul Nissen

doi:10.1038/s41467-018-06787-w

Nature Communications (Oct 2018)

Dimethyl fumarate is an allosteric covalent inhibitor of the p90 ribosomal S6 kinases

Jacob Lauwring Andersen,
Borbala Gesser,
Erik Daa Funder,
Christine Juul Fælled Nielsen,
Helle Gotfred-Rasmussen,
Mads Kirchheiner Rasmussen,
Rachel Toth,
Kurt Vesterager Gothelf,
J. Simon C. Arthur,
Lars Iversen,
Poul Nissen

Affiliations

Jacob Lauwring Andersen: Danish Research Institute of Translational Neuroscience – DANDRITE, Nordic-EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University
Borbala Gesser: Department of Dermatology, Aarhus University Hospital
Erik Daa Funder: Department of Chemistry and iNANO, Aarhus University
Christine Juul Fælled Nielsen: Danish Research Institute of Translational Neuroscience – DANDRITE, Nordic-EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University
Helle Gotfred-Rasmussen: Danish Research Institute of Translational Neuroscience – DANDRITE, Nordic-EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University
Mads Kirchheiner Rasmussen: Department of Dermatology, Aarhus University Hospital
Rachel Toth: Division of Cell Signaling and Immunology and University of Dundee
Kurt Vesterager Gothelf: Department of Chemistry and iNANO, Aarhus University
J. Simon C. Arthur: Division of Cell Signaling and Immunology and University of Dundee
Lars Iversen: Department of Dermatology, Aarhus University Hospital
Poul Nissen: Danish Research Institute of Translational Neuroscience – DANDRITE, Nordic-EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University

DOI: https://doi.org/10.1038/s41467-018-06787-w
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 8

Abstract

Read online

Dimethyl fumarate (DMF) is a major drug in the treatment of psoriasis and multiple sclerosis. Here the authors reveal a mechanism of RSK/MSK inhibition through covalent inhibition that can explain the observed clinical effects and the dose–response characteristics of DMF treatment.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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