Inhibition of geranylgeranyl transferase-I decreases cell viability of HTLV-1-transformed cells.
Viruses
; 3(10): 1815-35, 2011 10.
Article
en En
| MEDLINE
| ID: mdl-22069517
Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), an aggressive and highly chemoresistant malignancy. Rho family GTPases regulate multiple signaling pathways in tumorigenesis: cytoskeletal organization, transcription, cell cycle progression, and cell proliferation. Geranylgeranylation of Rho family GTPases is essential for cell membrane localization and activation of these proteins. It is currently unknown whether HTLV-1-transformed cells are preferentially sensitive to geranylgeranylation inhibitors, such as GGTI-298. In this report, we demonstrate that GGTI-298 decreased cell viability and induced G(2)/M phase accumulation of HTLV-1-transformed cells, independent of p53 reactivation. HTLV-1-LTR transcriptional activity was inhibited and Tax protein levels decreased following treatment with GGTI-298. Furthermore, GGTI-298 decreased activation of NF-κB, a downstream target of Rho family GTPases. These studies suggest that protein geranylgeranylation contributes to dysregulation of cell survival pathways in HTLV-1-transformed cells.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Benzamidas
/
Virus Linfotrópico T Tipo 1 Humano
/
Transducción de Señal
/
Prenilación de Proteína
/
Transferasas Alquil y Aril
Límite:
Humans
Idioma:
En
Revista:
Viruses
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Suiza