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Protein prenylation...
Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions
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- Akula, Murali K (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Ibrahim, Mohamed X (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Sahlgrenska Cancer Center,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Ivarsson, Emil G., 1989 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Khan, O. M. (author)
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- Kumar, Israiel T. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Sahlgrenska Cancer Center,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Erlandsson, Malin, 1972 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Karlsson, Christin, 1956 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Xu, X. F. (author)
- Karolinska Institutet
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- Brisslert, Mikael, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Brakebusch, C. (author)
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Wang, D. (author)
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- Bokarewa, Maria, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Sayin, Volkan I., 1983 (author)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Sahlgrenska Cancer Center,Institute of Clinical Sciences, Department of Surgery
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- Bergö, Martin O., 1970 (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Sahlgrenska Cancer Center,Institute of Medicine, Department of Molecular and Clinical Medicine
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(creator_code:org_t)
- 2019-09-04
- 2019
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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https://www.nature.c...
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Abstract
Subject headings
Close
- Rho family proteins are prenylated by geranylgeranyltransferase type I (GGTase-I), which normally target proteins to membranes for GTP-loading. However, conditional deletion of GGIase-I in mouse macrophages increases GTP-loading of Rho proteins, leading to enhanced inflammatory responses and severe rheumatoid arthritis. Here we show that heterozygous deletion of the Rho family gene Rac1, but not Rhoa and Cdc42, reverses inflammation and arthritis in GGTase-I-deficient mice. Non-prenylated Rac1 has a high affinity for the adaptor protein Ras GTPase-activating-like protein 1 (Iqgap1), which facilitates both GTP exchange and ubiquitination-mediated degradation of Rac1. Consistently, inactivating lagapl normalizes Rac1 GTP-loading, and reduces inflammation and arthritis in GGTase-I-deficient mice, as well as prevents statins from increasing Rac1 GTP-loading and cytokine production in macrophages. We conclude that blocking prenylation stimulates Rac1 effector interactions and unleashes proinflammatory signaling. Our results thus suggest that prenylation normally restrains innate immune responses by preventing Rac1 effector interactions.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- central-nervous-system
- rho-gtpases
- progenitor
- statins
- cdc42
- identification
- secretion
- promotes
- disease
- binding
- Science & Technology - Other Topics
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Akula, Murali K
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Ibrahim, Mohamed ...
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Ivarsson, Emil G ...
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Khan, O. M.
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Kumar, Israiel T ...
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Erlandsson, Mali ...
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show more...
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Karlsson, Christ ...
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Xu, X. F.
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Brisslert, Mikae ...
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Brakebusch, C.
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Wang, D.
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Bokarewa, Maria, ...
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Sayin, Volkan I. ...
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Bergö, Martin O. ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Nature Communica ...
- By the university
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University of Gothenburg
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Karolinska Institutet