Role of ATF4 in skeletal muscle atrophy.

Abstract:

PURPOSE OF REVIEW:Here, we discuss recent work focused on the role of activating transcription factor 4 (ATF4) in skeletal muscle atrophy. RECENT FINDINGS: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. SUMMARY: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.

authors

Adams CM,Ebert SM,Dyle MC

doi

10.1097/MCO.0000000000000362

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

164-168

issue

3

eissn

1363-1950

issn

1473-6519

pii

00075197-201705000-00004

journal_volume

20

pub_type

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