NF-κB but not FoxO sites in the MuRF1 promoter are required for transcriptional activation in disuse muscle atrophy.
Am J Physiol Cell Physiol
; 306(8): C762-7, 2014 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-24553183
ABSTRACT
The muscle-specific ring finger protein 1 (MuRF1) gene is required for most types of skeletal muscle atrophy yet we have little understanding of its transcriptional regulation. The purpose of this study is to identify whether NF-κB and/or FoxO response elements in the MuRF1 promoter are required for MuRF1 gene activation during skeletal muscle atrophy due to the removal of hindlimb weight bearing ("unloading"). Both NF-κB -dependent and FoxO-dependent luciferase reporter activities were significantly increased at 5 days of unloading. Using a 4.4-kb MuRF1 promoter reporter construct, a fourfold increase in reporter (i.e., luciferase) activity was found in rat soleus muscles after 5 days of hindlimb unloading. This activation was abolished by mutagenesis of either of the two distal putative NF-κB sites or all three putative NF-κB sites but not by mutagenesis of all four putative FoxO sites. This work provides the first direct evidence that NF-κB sites, but not FoxO sites, are required for MuRF1 promoter activation in muscle disuse atrophy in vivo.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Atrofia Muscular
/
Activación Transcripcional
/
FN-kappa B
/
Ubiquitina-Proteína Ligasas
/
Factores de Transcripción Forkhead
/
Proteínas Musculares
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Asunto de la revista:
FISIOLOGIA
Año:
2014
Tipo del documento:
Article