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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Roberts, Benjamin Artigues, Antonio Weinman, Steven A. Tikhanovich, Irina Villar, Maria T. Kuravi, Sudhakiranmayi Dorko, Kenneth Nawabi, Atta |
| Description | Author Affiliation: Tikhanovich I ( From the Department of Internal Medicine.); Kuravi S ( From the Department of Internal Medicine.); Artigues A ( Department of Biochemistry and Molecular Biology, and.); Villar MT ( Department of Biochemistry and Molecular Biology, and.); Dorko K ( Department of Pharmacology and Toxicology, University of Kansas Medical Center, Kansas City, Kansas 66160.); Nawabi A ( Department of Surgery.); Roberts B ( From the Department of Internal Medicine.); Weinman SA ( From the Department of Internal Medicine, sweinman@kumc.edu.) |
| Abstract | Arginine methylation is a common post-translational modification, but its role in regulating protein function is poorly understood. This study demonstrates that, TNF receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase involved in innate immune signaling, is regulated by reversible arginine methylation in a range of primary and cultured cells. Under basal conditions, TRAF6 is methylated by the methyltransferase PRMT1, and this inhibits its ubiquitin ligase activity, reducing activation of toll-like receptor signaling. In response to toll-like receptor ligands, TRAF6 is demethylated by the Jumonji domain protein JMJD6. Demethylation is required for maximal activation of NF-κB. Loss of JMJD6 leads to reduced response, and loss of PRMT1 leads to basal pathway activation with subsequent desensitization to ligands. In human primary cells, variations in the PRMT1/JMJD6 ratio significantly correlate with TRAF6 methylation, basal activation of NF-κB, and magnitude of response to LPS. Reversible arginine methylation of TRAF6 by the opposing effects of PRMT1 and JMJD6 is, therefore, a novel mechanism for regulation of innate immune pathways. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 36 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-09-04 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Arginine Metabolism Signal Transduction TNF Receptor-Associated Factor 6 Toll-Like Receptors Animals Blotting, Western Cell Line Cell Line, Tumor Cells, Cultured Interleukin-1 Receptor-Associated Kinases Genetics Jumonji Domain-Containing Histone Demethylases Kinetics Ligands Methylation Mice, Inbred C57BL NF-kappa B Protein-Arginine N-Methyltransferases RNA Interference Repressor Proteins Ubiquitin-Protein Ligases Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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