The E3 ubiquitin ligase SPOP controls resolution of systemic inflammation by triggering MYD88 degradation.
Nat Immunol
; 20(9): 1196-1207, 2019 09.
Article
en En
| MEDLINE
| ID: mdl-31406379
ABSTRACT
The response to systemic infection and injury requires the rapid adaptation of hematopoietic stem cells (HSCs), which proliferate and divert their differentiation toward the myeloid lineage. Significant interest has emerged in understanding the signals that trigger the emergency hematopoietic program. However, the mechanisms that halt this response of HSCs, which is critical to restore homeostasis, remain unknown. Here we reveal that the E3 ubiquitin ligase Speckle-type BTB-POZ protein (SPOP) restrains the inflammatory activation of HSCs. In the absence of Spop, systemic inflammation proceeded in an unresolved manner, and the sustained response in the HSCs resulted in a lethal phenotype reminiscent of hyper-inflammatory syndrome or sepsis. Our proteomic studies decipher that SPOP restricted inflammation by ubiquitinating the innate signal transducer myeloid differentiation primary response protein 88 (MYD88). These findings unearth an HSC-intrinsic post-translational mechanism that is essential for reestablishing homeostasis after emergency hematopoiesis.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
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Proteínas Nucleares
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Factor 88 de Diferenciación Mieloide
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Inflamación
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Leucocitosis
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Neutrófilos
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos