Role of ATF4 in skeletal muscle atrophy
Autor: | Christopher M. Adams, Michael C. Dyle, Scott M. Ebert |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Aging Muscle Fibers Skeletal Medicine (miscellaneous) Activating Transcription Factor 4 Bioinformatics Immobilization 03 medical and health sciences 0302 clinical medicine Atrophy Gene expression Animals Humans Medicine Muscle Skeletal Muscle contracture Nutrition and Dietetics business.industry ATF4 Skeletal muscle Fasting medicine.disease Muscular Atrophy 030104 developmental biology medicine.anatomical_structure business 030217 neurology & neurosurgery Signal Transduction Skeletal muscle atrophy |
Zdroj: | Current Opinion in Clinical Nutrition & Metabolic Care. 20:164-168 |
ISSN: | 1363-1950 |
Popis: | Here, we discuss recent work focused on the role of activating transcription factor 4 (ATF4) in skeletal muscle atrophy.Muscle atrophy involves and requires widespread changes in skeletal muscle gene expression; however, the transcriptional regulatory proteins responsible for those changes are not yet well defined. Recent work indicates that some forms of muscle atrophy require ATF4, a stress-inducible bZIP transcription factor subunit that helps to mediate a broad range of stress responses in mammalian cells. ATF4 expression in skeletal muscle fibers is sufficient to induce muscle fiber atrophy and required for muscle atrophy during several stress conditions, including aging, fasting, and limb immobilization. By helping to activate specific genes in muscle fibers, ATF4 contributes to the expression of numerous mRNAs, including at least two mRNAs (Gadd45a and p21) that encode mediators of muscle fiber atrophy. Gadd45a promotes muscle fiber atrophy by activating the protein kinase MEKK4. p21 promotes atrophy by reducing expression of spermine oxidase, a metabolic enzyme that helps to maintain muscle fiber size under nonstressed conditions.In skeletal muscle fibers, ATF4 is critical component of a complex and incompletely understood molecular signaling network that causes muscle atrophy during aging, fasting, and immobilization. |
Databáze: | OpenAIRE |
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