2012
DOI: 10.1074/jbc.m112.374777
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Stress-induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy

Abstract: Background:In skeletal muscle, diverse stresses induce the transcription factor ATF4, which promotes muscle atrophy by an unknown mechanism. Results: ATF4 causes muscle atrophy by inducing Gadd45a, which reprograms myonuclear gene expression to repress antiatrophy mechanisms and induce pro-atrophy mechanisms. Conclusion: Gadd45a is a critical stress-induced mediator of muscle atrophy. Significance: The ATF4/Gadd45a pathway is a potential therapeutic target in atrophic muscle.

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Cited by 195 publications
(344 citation statements)
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“…PERK deficiency in mice results in diabetes mellitus, skeletal dysplasias, and growth retardation [23,24], whereas ATF4 deficiency in mice causes microphthalmia [25,26], anemia [27], and bone angiogenesis deficits [28]. Interestingly, ATF4 deficiency protects mice from ER-stress-induced tissue damage [29][30][31]. Similar protective phenotypes were also observed in CHOP deficient mice [16,32,33].…”
Section: Introductionsupporting
confidence: 53%
“…PERK deficiency in mice results in diabetes mellitus, skeletal dysplasias, and growth retardation [23,24], whereas ATF4 deficiency in mice causes microphthalmia [25,26], anemia [27], and bone angiogenesis deficits [28]. Interestingly, ATF4 deficiency protects mice from ER-stress-induced tissue damage [29][30][31]. Similar protective phenotypes were also observed in CHOP deficient mice [16,32,33].…”
Section: Introductionsupporting
confidence: 53%
“…Atf4 conditional KO ( lox/lox ) mice and SMMHC-Cre ER(T2) mice were generated as previously described (10,49,50). SMMHC-Cre/GFP global Atf4 +/-and DBA/2J mice were obtained from The Jackson Laboratory (51,52).…”
Section: Methodsmentioning
confidence: 99%
“…1, A and B). GADD45A responds to cell stress and regulates anabolic signaling and energy homeostasis (19). P21 induces cell cycle arrest (30) and suppresses proliferation of multiple cell types in the skeletal muscle tissue (6); downstream, p21-activated kinase enhances cytoskeletal remodeling and glucose uptake (73).…”
Section: Transitory Cytostasismentioning
confidence: 99%