Post-translational control of T cell development by the ESCRT protein CHMP5.
Nat Immunol
; 18(7): 780-790, 2017 Jul.
Article
en En
| MEDLINE
| ID: mdl-28553951
ABSTRACT
The acquisition of a protective vertebrate immune system hinges on the efficient generation of a diverse but self-tolerant repertoire of T cells by the thymus through mechanisms that remain incompletely resolved. Here we identified the endosomal-sorting-complex-required-for-transport (ESCRT) protein CHMP5, known to be required for the formation of multivesicular bodies, as a key sensor of thresholds for signaling via the T cell antigen receptor (TCR) that was essential for T cell development. CHMP5 enabled positive selection by promoting post-selection thymocyte survival in part through stabilization of the pro-survival protein Bcl-2. Accordingly, loss of CHMP5 in thymocyte precursor cells abolished T cell development, a phenotype that was 'rescued' by genetic deletion of the pro-apoptotic protein Bim or transgenic expression of Bcl-2. Mechanistically, positive selection resulted in the stabilization of CHMP5 by inducing its interaction with the deubiquitinase USP8. Our results thus identify CHMP5 as an essential component of the post-translational machinery required for T cell development.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Receptores de Antígenos de Linfocitos T
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Linfocitos T
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Diferenciación Celular
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Complejos de Clasificación Endosomal Requeridos para el Transporte
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Timocitos
Límite:
Animals
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos