Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions

Murali K. Akula; Mohamed X. Ibrahim; Emil G. Ivarsson; Omar M. Khan; Israiel T. Kumar; Malin Erlandsson; Christin Karlsson; Xiufeng Xu; Mikael Brisslert; Cord Brakebusch; Donghai Wang; Maria Bokarewa; Volkan I. Sayin; Martin O. Bergo

doi:10.1038/s41467-019-11606-x

Nature Communications (Sep 2019)

Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions

Murali K. Akula,
Mohamed X. Ibrahim,
Emil G. Ivarsson,
Omar M. Khan,
Israiel T. Kumar,
Malin Erlandsson,
Christin Karlsson,
Xiufeng Xu,
Mikael Brisslert,
Cord Brakebusch,
Donghai Wang,
Maria Bokarewa,
Volkan I. Sayin,
Martin O. Bergo

Affiliations

Murali K. Akula: Sahlgrenska Cancer Center, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg
Mohamed X. Ibrahim: Sahlgrenska Cancer Center, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg
Emil G. Ivarsson: Sahlgrenska Cancer Center, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg
Omar M. Khan: Adult Stem Cell Laboratory, Francis Crick Research Institute
Israiel T. Kumar: Sahlgrenska Cancer Center, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg
Malin Erlandsson: Department of Rheumatology, Institute of Medicine, University of Gothenburg
Christin Karlsson: Sahlgrenska Cancer Center, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg
Xiufeng Xu: Department of Biosciences and Nutrition, Karolinska Institutet
Mikael Brisslert: Department of Rheumatology, Institute of Medicine, University of Gothenburg
Cord Brakebusch: Biotech Research and Innovation Centre, University of Copenhagen
Donghai Wang: Department of Immunology, Duke University School of Medicine
Maria Bokarewa: Department of Rheumatology, Institute of Medicine, University of Gothenburg
Volkan I. Sayin: Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg
Martin O. Bergo: Sahlgrenska Cancer Center, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg

DOI: https://doi.org/10.1038/s41467-019-11606-x
Journal volume & issue: Vol. 10, no. 1
pp. 1 – 13

Abstract

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Macrophage specific deletion of GGTase-I, a prenylation enzyme, in mice induces inflammatory response and rheumatoid arthritis. Here the authors show that GGTase-I deficiency and the resulting reduction of RAC1 prenylation increase RAC1 interaction with the adaptor protein IQGAP1, leading to GTP-loading of RAC1 and enhanced proinflammatory cytokine production.

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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