Wild-type AIRE cooperates with p63 in HLA class II expression of medullary thymic stromal cells.
Biochem Biophys Res Commun
; 379(3): 765-70, 2009 Feb 13.
Article
en En
| MEDLINE
| ID: mdl-19124002
During T cell development in the thymus, autoreactive T cells are deleted through a mechanism that is actively supported by medullary epithelial cells. These epithelial cells possess particular transcription factors including autoimmune regulator (AIRE), which is responsible for regulating expression of self-antigens, as well as p63, a p53-like molecule. Here we present evidence suggesting interaction of AIRE with p63 through a SAND domain and a transactivation domain, respectively. Interestingly an AIRE molecule with a mutated SAND domain of G228W, whose genetic alteration is inherited in an autosomal dominant manner, could not establish a complex with p63 as indicated by immunoprecipitation and molecular modeling analyses. Further in vitro study indicated that the G228W mutation led to downregulation of the transcription levels of CIITA and, accordingly, the cell surface expression of HLA class II molecules in thymic epithelial cells with p63. This indicates novel involvement of AIRE and p63 in the regulation of HLA class II, and suggests that defects in the AIRE-p63 interaction may lead to malfunction of HLA-based selection of self-reactive helper CD4(+) T cells in the thymus.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Timo
/
Factores de Transcripción
/
Antígenos de Histocompatibilidad Clase II
/
Transactivadores
/
Proteínas Supresoras de Tumor
Tipo de estudio:
Prognostic_studies
Límite:
Child, preschool
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2009
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos