A20 targets caspase-8 and FADD to protect HTLV-I-infected cells.
Leukemia
; 30(3): 716-27, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26437781
ABSTRACT
Adult T-cell leukemia (ATL) arises from a human T-cell leukemia virus type I (HTLV-I)-infected cell and has few therapeutic options. Here, we have uncovered a previously unrecognized role for a ubiquitin-editing enzyme A20 in the survival of HTLV-I-infected cells. Unlike in lymphomas of the B-cell lineage, A20 is abundantly expressed in primary ATL cells without notable mutations. Depletion of A20 in HTLV-I-infected cells resulted in caspase activation, cell death induction and impaired tumorigenicity in mouse xenograft models. Mechanistically, A20 stably interacts with caspase-8 and Fas-associated via death domain (FADD) in HTLV-I-infected cells. Mutational studies revealed that A20 supports the growth of HTLV-I-infected cells independent of its catalytic functions and that the zinc-finger domains are required for the interaction with and regulation of caspases. These results indicate a pivotal role for A20 in the survival of HTLV-I-infected cells and implicate A20 as a potential therapeutic target in ATL.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Vírus Linfotrópico T Tipo 1 Humano
/
Leucemia-Linfoma de Células T do Adulto
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Proteínas de Ligação a DNA
/
Caspase 8
/
Proteína de Domínio de Morte Associada a Fas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Leukemia
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Japão