MARCH3 attenuates IL-1ß-triggered inflammation by mediating K48-linked polyubiquitination and degradation of IL-1RI.
Proc Natl Acad Sci U S A
; 115(49): 12483-12488, 2018 12 04.
Article
en En
| MEDLINE
| ID: mdl-30442668
ABSTRACT
The proinflammatory cytokine IL-1ß plays critical roles in inflammatory and autoimmune diseases. IL-1ß signaling is tightly regulated to avoid excessive inflammatory response. In this study, we identified the E3 ubiquitin ligase membrane-associated RING-CH-type finger 3 (MARCH3) as a critical negative regulator of IL-1ß-triggered signaling. Overexpression of MARCH3 inhibited IL-1ß-triggered activation of NF-κB as well as expression of inflammatory genes, whereas MARCH3 deficiency had the opposite effects. MARCH3-deficient mice produced higher levels of serum inflammatory cytokines and were more sensitive to inflammatory death upon IL-1ß injection or Listeria monocytogenes infection. Mechanistically, MARCH3 was associated with IL-1 receptor I (IL-1RI) and mediated its K48-linked polyubiquitination at K409 and lysosomal-dependent degradation. Furthermore, IL-1ß stimulation triggered dephosphorylation of MARCH3 by CDC25A and activation of its E3 ligase activity. Our findings suggest that MARCH3-mediated IL-1RI degradation is an important mechanism for attenuating IL-1ß-triggered inflammatory response.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos y Proteínas de Señalización Intracelular
/
Interleucina-1beta
/
Receptores Tipo I de Interleucina-1
/
Inflamación
/
Listeriosis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2018
Tipo del documento:
Article
País de afiliación:
China