Ubiquitin Ligase TRIM62 Regulates CARD9-Mediated Anti-fungal Immunity and Intestinal Inflammation.
Immunity
; 43(4): 715-26, 2015 Oct 20.
Article
en En
| MEDLINE
| ID: mdl-26488816
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de Angiotensina
/
Receptores de Endotelina
/
Ubiquitina-Proteína Ligasas
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Proteínas Adaptadoras de Señalización CARD
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Candidiasis Invasiva
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos