Description:
<jats:p>The mammalian target of rapamycin complex 1/S6 ribosomal protein kinase 1 (mTORC1/S6K1) pathway is a critical regulator of mRNA translation and skeletal muscle mass. It does this in part by inhibiting the tumor suppressor protein, programmed cell death 4 (PDCD4). In C2C12 and L6 muscle cells, we showed that PDCD4 abundance was high on day 1 and then decreased as myoblasts differentiated into myotubes (p<0.05). siRNA‐mediated knockdown of S6K1 reversed the decrease in PDCD4 abundance and significantly decreased myosin heavy chain 1 (MHC 1) protein abundance, suggesting that PDCD4 regulation was vital for differentiation. Indeed, cells depleted of PDCD4 had reduced MHC abundance, showed delayed myoblast fusion and abnormal myotube formation. On days 3 and 4 of differentiation, myotubes depleted of PDCD4 showed 40–60% reductions in myotube protein synthesis. This study unravels a link between PDCD4 and muscle cell differentiation, and suggests that this mTORC1/S6K1 substrate may be of therapeutic significance for muscle recovery following injury or atrophy. Funded by NSERC.</jats:p>