Nijmegen breakage syndrome fibroblasts expressing the C-terminal truncated NBN(p70) protein undergo p38/MK2-dependent premature senescence.
Biogerontology
; 16(1): 43-51, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25214013
ABSTRACT
Fibroblasts from the progeroid Nijmegen breakage syndrome that express a truncated version of the nibrin protein (NBN(p70)) undergo premature senescence and have an enlarged morphology with high levels of senescence-associated ß-galactosidase, although they do not have F-actin stress fibres. Growth of these fibroblasts in the continuous presence of p38 inhibitors resulted in a large increase in replicative capacity and changed the cellular morphology so that the cells resembled young normal fibroblasts. A similar effect was seen using an inhibitor of the p38 downstream effector kinase MK2. These data suggest that NBN(p70) expressing cells undergo a degree of stress-induced replicative senescence via p38/MK2 activation, potentially due to increased telomere dysfunction, that may play a role in the progeroid features seen in this syndrome.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Transducción de Señal
/
Senescencia Celular
/
Proteínas Serina-Treonina Quinasas
/
Proteínas de Ciclo Celular
/
Proteínas Quinasas p38 Activadas por Mitógenos
/
Péptidos y Proteínas de Señalización Intracelular
/
Síndrome de Nijmegen
/
Fibroblastos
Límite:
Humans
Idioma:
En
Revista:
Biogerontology
Asunto de la revista:
GERIATRIA
Año:
2015
Tipo del documento:
Article