An inducible system for in vitro and in vivo Fas activation using FKBP-FRB-rapamycin complex.
Biochem Biophys Res Commun
; 523(2): 473-480, 2020 03 05.
Article
en En
| MEDLINE
| ID: mdl-31882118
ABSTRACT
The inducible activation system is valuable for investigating spatiotemporal roles of molecules. A chemically inducible activation system for Fas (CD95/APO-1), which works efficiently to induce apoptosis and leads non-apoptotic pathways, has not yet been developed. Here, we engineered a rapamycin-induced dimerization system of Fas consisting of FKBP and FRB proteins. Treatment of rapamycin specifically induces cellular apoptosis. In neurons and cells with high c-FLIP expression, rapamycin-induced Fas activation triggered the activation of the non-apoptotic pathway components instead of cell death. Intracranial delivery of the system could be utilized to induce apoptosis of tumor cells upon rapamycin treatment. Our results demonstrate a novel inducible Fas activation system which operates with high efficiency and temporal precision in vitro and in vivo promising a potential therapeutic strategy.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ingeniería de Proteínas
/
Receptor fas
/
Sirolimus
/
Proteínas de Unión a Tacrolimus
/
Proteína 1A de Unión a Tacrolimus
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2020
Tipo del documento:
Article