Ubiquitin Ligase TRIM62 Regulates CARD9-Mediated Anti-fungal Immunity and Intestinal Inflammation
| Autor: | Cisca Wijmenga, Terry K. Means, Robert J. Heath, Agnes Gardet, Zhifang Cao, Aylwin Ng, Mark J. Daly, Elizaveta S. Leshchiner, Jason S. Rush, Hailiang Huang, Alykhan F. Shamji, Natalia B. Nedelsky, John D. Rioux, Mihai G. Netea, Kara L. Conway, Ramnik J. Xavier, Shih-Chin Cheng, Zaida G. Ramirez-Ortiz |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI) |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_treatment
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Tripartite Motif Proteins Mice Ubiquitin Protein Interaction Mapping Immunology and Allergy Protein Isoforms Receptor Genes Dominant Mice Knockout Receptors Angiotensin biology Receptors Endothelin Colitis CROHNS-DISEASE 3. Good health Ubiquitin ligase Cell biology Specific Pathogen-Free Organisms INHERITED CARD9 DEFICIENCY Infectious Diseases Cytokine Cytokines Signal transduction Signal Transduction Mice 129 Strain Recombinant Fusion Proteins Ubiquitin-Protein Ligases Immunology COLITIS SUSCEPTIBILITY LOCI DENDRITIC CELLS Article Adjuvants Immunologic Immunity FUNGAL-INFECTIONS medicine Animals Humans Candidiasis Invasive Genetic Predisposition to Disease BOWEL-DISEASE DEEP DERMATOPHYTOSIS CANDIDA-ALBICANS Innate immune system HEK 293 cells ANTIVIRAL RESPONSE Ubiquitination Inflammatory Bowel Diseases Protein Structure Tertiary CARD Signaling Adaptor Proteins HEK293 Cells biology.protein INNATE IMMUNITY Protein Processing Post-Translational HeLa Cells |
| Zdroj: | Immunity, 43, 715-26 Immunity, 43(4), 715-726. CELL PRESS Immunity, 43, 4, pp. 715-26 |
| ISSN: | 1074-7613 |
| Popis: | Contains fulltext : 152899.pdf (Publisher’s version ) (Closed access) CARD9 is a central component of anti-fungal innate immune signaling via C-type lectin receptors, and several immune-related disorders are associated with CARD9 alterations. Here, we used a rare CARD9 variant that confers protection against inflammatory bowel disease as an entry point to investigating CARD9 regulation. We showed that the protective variant of CARD9, which is C-terminally truncated, acted in a dominant-negative manner for CARD9-mediated cytokine production, indicating an important role for the C terminus in CARD9 signaling. We identified TRIM62 as a CARD9 binding partner and showed that TRIM62 facilitated K27-linked poly-ubiquitination of CARD9. We identified K125 as the ubiquitinated residue on CARD9 and demonstrated that this ubiquitination was essential for CARD9 activity. Furthermore, we showed that similar to Card9-deficient mice, Trim62-deficient mice had increased susceptibility to fungal infection. In this study, we utilized a rare protective allele to uncover a TRIM62-mediated mechanism for regulation of CARD9 activation. |
| Databáze: | OpenAIRE |
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