Why the study?
Rapamycin-sensitive signaling is implicated in mechanical signal-induced muscle mass increases, but rapamycin-insensitive events are also involved and remain to be identified.
TRIM28 phosphorylation at S473 is identified as a major rapamycin-insensitive signaling event that regulates skeletal muscle hypertrophy in response to mechanical loading.
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TRIM28 S473 phosphorylation regulates hypertrophy via rapamycin-insensitive signaling in mice; leaves open whether it offers new targets for human muscle disorders.
Mechanical signals, such as those evoked by maximal-intensity contractions (MICs), can induce an increase in muscle mass. Rapamycin-sensitive signaling events are widely implicated in the regulation of this process; however, recent studies indicate that rapamycin-insensitive signaling events are also involved. Thus, to identify these events, we generate a map of the MIC-regulated and rapamycin-sensitive phosphoproteome. In total, we quantify more than 10,000 unique phosphorylation sites and find that more than 2,000 of these sites are significantly affected by MICs, but remarkably, only 38 of the MIC-regulated events are mediated through a rapamycin-sensitive mechanism. Further interrogation of the rapamycin-insensitive phosphorylation events identifies the S473 residue on Tripartite Motif-Containing 28 (TRIM28) as one of the most robust MIC-regulated phosphorylation sites, and extensive follow-up studies suggest that TRIM28 significantly contributes to the homeostatic regulation of muscle size and function as well as the hypertrophy that occurs in response to increased mechanical loading.
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Steinert et al. (2021) studied this question.
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