Signal-dependent fra-2 regulation in skeletal muscle reserve and satellite cells.
Cell Death Dis
; 4: e692, 2013 Jun 27.
Article
in En
| MEDLINE
| ID: mdl-23807221
ABSTRACT
Activator protein-1 (AP-1) is a ubiquitous transcription factor that paradoxically also has some tissue-specific functions. In skeletal muscle cells, we document that the AP-1 subunit, Fra-2, is expressed in the resident stem cells (Pax7-positive satellite cells) and also in the analogous undifferentiated 'reserve' cell population in myogenic cultures, but not in differentiated myofiber nuclei. Silencing of Fra-2 expression enhances the expression of differentiation markers such as muscle creatine kinase and myosin heavy chain, indicating a possible role of Fra-2 in undifferentiated myogenic progenitor cells. We observed that Fra-2 is a target of cytokine-mediated extracellular signal-regulated kinase-1/2 signaling in cultured muscle cells, and extensive mass spectrometry and mutational analysis identified S320 and T322 as regulators of Fra-2 protein stability. Interestingly, Fra-2 S320 phosphorylation occurs transiently in activated satellite cells and is extinguished in myogenin-positive differentiating cells. Thus, cytokine-mediated Fra-2 expression and stabilization is linked to regulation of myogenic progenitor cells having implications for the molecular regulation of adult muscle stem cells and skeletal muscle regeneration.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
MAP Kinase Signaling System
/
Satellite Cells, Skeletal Muscle
/
Fos-Related Antigen-2
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Cell Death Dis
Year:
2013
Document type:
Article
Affiliation country:
Canada