The Transcription Factor ATF4 Promotes Skeletal Myofiber Atrophy during Fasting

摘要: Prolonged fasting alters skeletal muscle gene expression in a manner that promotes myofiber atrophy, but the underlying mechanisms are not fully understood. Here, we examined potential role of activating transcription factor 4 (ATF4), with an evolutionarily ancient cellular response to starvation. In mouse muscle, increases level ATF4 mRNA. To determine whether increased was required for reduced inhibitory RNA targeting and found it atrophy during fasting. Likewise, reducing mRNA phosphorylation-resistant form eukaryotic initiation 2α decreased atrophy. sufficient reduce size, overexpressed size absence contrast, transcriptionally inactive construct did suggesting requirement ATF4-mediated transcriptional regulation. begin mechanism compared effects overexpression on global expression. Interestingly, small subset five fasting-responsive mRNAs, including four 15 mRNAs most highly induced by These encode proteins previously implicated growth suppression (p21Cip1/Waf1, GADD45α, PW1/Peg3) or titin-based stress signaling [muscle LIM protein (MLP) cardiac ankyrin repeat (CARP)]. Taken together, these data identify as novel mediator