Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Oncogene ; 35(32): 4269-81, 2016 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-26776161

RESUMEN

Constitutive activation of the antiapoptotic nuclear factor-κB (NF-κB) signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL). Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-κB pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 in the NF-κB negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of ß-catenin and its destruction complex consisting of APC, AXIN1, CK1α and GSK3ß to oncogenic CARMA1. Recruitment of the ß-catenin destruction complex was independent of CARMA1-BCL10-MALT1 complex formation or constitutive NF-κB activation and promoted the stabilization of ß-catenin. The ß-catenin destruction complex was also recruited to CARMA1 in ABC DLBCL cell lines, which coincided with elevated ß-catenin expression. In line, ß-catenin was frequently detected in non-GCB DLBCL biopsies that rely on chronic BCR signaling. Increased ß-catenin amounts alone were not sufficient to induce classical WNT target gene signatures, but could augment TCF/LEF-dependent transcriptional activation in response to WNT signaling. In conjunction with NF-κB, ß-catenin enhanced expression of immunosuppressive interleukin-10 and suppressed antitumoral CCL3, indicating that ß-catenin can induce a favorable tumor microenvironment. Thus, parallel activation of NF-κB and ß-catenin signaling by gain-of-function mutations in CARMA1 augments WNT stimulation and is required for regulating the expression of distinct NF-κB target genes to trigger cell-intrinsic and extrinsic processes that promote DLBCL lymphomagenesis.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD/genética , Proteínas Adaptadoras de Señalización CARD/metabolismo , Carcinogénesis , Guanilato Ciclasa/genética , Guanilato Ciclasa/metabolismo , Linfoma de Células B Grandes Difuso/metabolismo , FN-kappa B/metabolismo , Transducción de Señal , beta Catenina/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Linfoma de Células B Grandes Difuso/patología , Mutación , Estabilidad Proteica , Factores de Transcripción TCF/metabolismo , Proteínas de Unión al GTP rho/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...