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Citations to this article

Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice
Omar M. Khan, … , Maria Bokarewa, Martin O. Bergo
Omar M. Khan, … , Maria Bokarewa, Martin O. Bergo
Published January 25, 2011
Citation Information: J Clin Invest. 2011;121(2):628-639. https://doi.org/10.1172/JCI43758.
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Research Article Article has an altmetric score of 1

Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice

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Abstract

RHO family proteins are important for the function of inflammatory cells. They are modified with a 20-carbon geranylgeranyl lipid in a process catalyzed by protein geranylgeranyltransferase type I (GGTase-I). Geranylgeranylation is viewed as essential for the membrane targeting and activity of RHO proteins. Consequently, inhibiting GGTase-I to interfere with RHO protein activity has been proposed as a strategy to treat inflammatory disorders. However, here we show that mice lacking GGTase-I in macrophages develop severe joint inflammation resembling erosive rheumatoid arthritis. The disease was initiated by the GGTase-I–deficient macrophages and was transplantable and reversible in bone marrow transplantation experiments. The cells accumulated high levels of active GTP-bound RAC1, CDC42, and RHOA, and RAC1 remained associated with the plasma membrane. Moreover, GGTase-I deficiency activated p38 and NF-κB and increased the production of proinflammatory cytokines. The results challenge the view that geranylgeranylation is essential for the activity and localization of RHO family proteins and suggest that reduced geranylgeranylation in macrophages can initiate erosive arthritis.

Authors

Omar M. Khan, Mohamed X. Ibrahim, Ing-Marie Jonsson, Christin Karlsson, Meng Liu, Anna-Karin M. Sjogren, Frida J. Olofsson, Mikael Brisslert, Sofia Andersson, Claes Ohlsson, Lillemor Mattsson Hultén, Maria Bokarewa, Martin O. Bergo

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Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2009 Total
Citations: 2 2 4 2 10 9 4 2 2 7 4 3 9 2 2 1 65
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