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Am J Physiol Cell Physiol. 2014 Apr 15;306(8):C762-7. doi: 10.1152/ajpcell.00361.2013. Epub 2014 Feb 19.

NF-κB but not FoxO sites in the MuRF1 promoter are required for transcriptional activation in disuse muscle atrophy.

Author information

1
Department of Health Sciences, Boston University, Boston, Massachusetts.

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.

KEYWORDS:

FoxO; MuRF1; NF-κB; muscle wasting; unloading

PMID:
24553183
PMCID:
PMC3989716
DOI:
10.1152/ajpcell.00361.2013
[Indexed for MEDLINE]
Free PMC Article

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