Degradation of p47 by autophagy contributes to CADM1 overexpression in ATLL cells through the activation of NF-κB.
Sci Rep
; 9(1): 3491, 2019 03 05.
Article
en En
| MEDLINE
| ID: mdl-30837480
ABSTRACT
Cell adhesion molecule 1 (CADM1), a member of the immunoglobulin superfamily, is identified as a novel cell surface marker for human T-cell leukemia virus (HTLV-1)-infected T cells. Adult T-cell leukemia/lymphoma (ATLL) is developed in HTLV-1-infected T-cells after a long infection period. To examine the mechanism of CADM1 overexpression in ATLL, we first identified that CADM1 is transcriptionally up-regulated by a transcriptional enhancer element through NF-κB signaling pathway. In HTLV-1-infected T-cells, CADM1 expression is dependent on HTLV-1/Tax through activation of canonical and non-canonical NF-κB; however, in ATLL cells with frequent loss of Tax expression, the activation of canonical NF-κB only enhances the CADM1 expression. Along with active mutations in signaling molecules under T-cell recepor (TCR) signaling, degradation of p47, a negative regulator of NF-κB, was essential for activation of canonical NF-κB through stabilization of NEMO (NF-κB essential modulator). The mechanism of p47 degradation is primarily dependent on activation of lysosomal-autophagy and the autophagy is activated in most of the HTLV-infected and ATLL cells, suggesting that the p47 degradation may be a first key molecular event during HTLV-1 infection to T-cells as a connector of two important signaling pathways, NF-κB and autophagy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Leucemia-Linfoma de Células T del Adulto
/
FN-kappa B
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Proteínas Adaptadoras Transductoras de Señales
/
Molécula 1 de Adhesión Celular
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón