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J Biol Chem ; 289(49): 34250-7, 2014 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-25331958

RESUMEN

B cell lymphoma 6 (BCL6) corepressor (BCOR) was discovered as a BCL6-interacting corepressor, but little is known about its other biological activities in normal B cell development and function. Previously, we found that interferon regulatory factor 8 (IRF8), also known as interferon consensus sequence-binding protein, directly targets a large number of genes in germinal center B cells including BCL6. In this study, we screened potential binding partners of IRF8 using a retrovirus-based protein complementation assay screen in a mouse pre-B cell line. We found that IRF8 interacts directly with BCOR and that the α-helical region of IRF8 and the BCL6 binding domain of BCOR are required for this interaction. In addition, IRF8 protein interacts directly with BCL6. Using an siRNA-mediated IRF8 knockdown mouse B cell lymphoma cell line, we showed that IRF8 represses Bcor and enhances Bcl6 transcription. Taken together, these data suggest that a complex comprising BCOR-BCL6-IRF8 modulates BCL6-associated transcriptional regulation of germinal center B cell function.


Asunto(s)
Núcleo Celular/metabolismo , Proteínas de Unión al ADN/genética , Regulación de la Expresión Génica , Factores Reguladores del Interferón/genética , Linfocitos/metabolismo , Proteínas Represoras/genética , Animales , Línea Celular Tumoral , Núcleo Celular/genética , Proteínas de Unión al ADN/metabolismo , Genes Reporteros , Vectores Genéticos , Células HEK293 , Humanos , Factores Reguladores del Interferón/antagonistas & inhibidores , Factores Reguladores del Interferón/metabolismo , Luciferasas/genética , Luciferasas/metabolismo , Linfocitos/citología , Ratones , Unión Proteica , Mapeo de Interacción de Proteínas , Proteínas Proto-Oncogénicas c-bcl-6 , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proteínas Represoras/metabolismo , Retroviridae/genética , Transducción de Señal , Transcripción Genética
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