NF-κB but not FoxO sites in the MuRF1 promoter are required for transcriptional activation in disuse muscle atrophy
| Autor: | Susan C. Kandarian, Robert W. Jackman, Chia-Ling Wu, Evangeline W. Cornwell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Transcriptional Activation
Physiology Ubiquitin-Protein Ligases Muscle Proteins Hindlimb Biology Tripartite Motif Proteins chemistry.chemical_compound Transcriptional regulation Animals Luciferase Promoter Regions Genetic Gene Regulation of gene expression Mutagenesis NF-kappa B NF-κB Forkhead Transcription Factors Cell Biology Articles NFKB1 Molecular biology Rats Muscular Atrophy chemistry Hindlimb Suspension Female |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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