RGD Reference Report - Multiple muscle wasting-related transcription factors are acetylated in dexamethasone-treated muscle cells. - Rat Genome Database

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Multiple muscle wasting-related transcription factors are acetylated in dexamethasone-treated muscle cells.

Authors: Chamberlain, W  Gonnella, P  Alamdari, N  Aversa, Z  Hasselgren, PO 
Citation: Chamberlain W, etal., Biochem Cell Biol. 2012 Apr;90(2):200-8. doi: 10.1139/o11-082. Epub 2012 Jan 31.
RGD ID: 7349318
Pubmed: (View Article at PubMed) PMID:22292478
DOI: Full-text: DOI:10.1139/o11-082

Recent studies suggest that the expression and activity of the histone acetyltransferase p300 are upregulated in catabolic muscle allowing for acetylation of cellular proteins. The function of transcription factors is influenced by posttranslational modifications, including acetylation. It is not known if transcription factors involved in the regulation of muscle mass are acetylated in atrophying muscle. We determined cellular levels of acetylated C/EBPbeta, C/EBPdelta, FOXO1, FOXO3a, and NF-kB/p65 in dexamethasone-treated L6 muscle cells, a commonly used in vitro model of muscle wasting. The role of p300 in dexamethasone-induced transcription factor acetylation and myotube atrophy was examined by transfecting muscle cells with p300 siRNA. Treatment of L6 myotubes with dexamethasone resulted in increased cellular levels of acetylated C/EBPbeta and delta, FOXO1 and 3a, and p65. Downregulation of p300 with p300 siRNA reduced acetylation of transcription factors and decreased dexamethasone-induced myotube atrophy and expression of the ubiquitin ligase MuRF1. The results suggest that several muscle wasting-related transcription factors are acetylated supporting the concept that posttranslational modifications of proteins regulating gene transcription may be involved in the loss of muscle mass. The results also suggest that acetylation of the transcription factors is at least in part regulated by p300 and plays a role in glucocorticoid-induced muscle atrophy. Targeting molecules that regulate acetylation of transcription factors may help reduce the impact of muscle wasting.



Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Ep300  (E1A binding protein p300)
Foxo3  (forkhead box O3)

Objects referenced in this article
Gene EP300 E1A binding protein p300 Homo sapiens
Gene Ep300 E1A binding protein p300 Mus musculus

Additional Information