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Updated: May 21, 2026
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In Situ Immunofluorescent Staining of Autophagy in Muscle Stem Cells
Published on: June 12, 2017
A direct HDAC4-MAP kinase crosstalk activates muscle atrophy program.
Moon-Chang Choi1, Todd J Cohen, Tomasa Barrientos
1Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Molecular Cell
|June 5, 2012
Summary
Histone deacetylase 4 (HDAC4) triggers muscle atrophy by activating the AP1 transcription factor through the MAPK pathway, not by repressing MEF2. This discovery reveals a novel signaling axis in neurogenic muscle atrophy.
Area of Science:
- Molecular Biology
- Cell Signaling
- Muscle Physiology
Background:
- Prolonged loss of neural input causes pathological muscle remodeling and atrophy.
- Histone deacetylase 4 (HDAC4) is crucial for activating the muscle atrophy program in denervated muscles.
- The precise signaling pathway linking HDAC4 to muscle atrophy machinery is not fully understood.
Purpose of the Study:
- To elucidate the signaling mechanism by which HDAC4 contributes to neurogenic muscle atrophy.
- To identify key molecular targets and pathways regulated by HDAC4 in muscle atrophy.
Main Methods:
- Investigated the role of AP1 transcription factor in HDAC4-mediated muscle atrophy.
- Examined the interaction and functional relationship between HDAC4 and AP1.
- Analyzed the involvement of the MAP kinase (MAPK) cascade in HDAC4 signaling.
- Assessed the deacetylation and activation of MEKK2 by HDAC4.
Main Results:
- HDAC4 activates AP1-dependent transcription in denervated muscle.
- AP1 inactivation mimics HDAC4 deficiency, mitigating the muscle atrophy program.
- HDAC4 activates AP1 independently of its repressor function, via the MAPK cascade.
- HDAC4 directly binds, deacetylates, and activates the MAP3 kinase, MEKK2.
Conclusions:
- An HDAC4-MAPK-AP1 signaling axis is essential for neurogenic muscle atrophy.
- HDAC4's role in atrophy involves crosstalk between acetylation and phosphorylation signaling.
- This study uncovers a novel mechanism regulating muscle atrophy.
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