N-Myc downstream-regulated gene 4 (NDRG4) plays an important role in biological processes and pathogenesis, but its function in muscle development is unclear. In this study, we investigated the function of the NDRG4 gene in the regulation of myogenic differentiation. NDRG4 expression is upregulated during muscle regeneration and C2C12 myoblast differentiation. Gain and loss of function studies revealed that NDRG4 dramatically promotes expression of myogenic differentiation factor (MyoD), myogenin (MyoG), and myosin heavy chain (MyHC) genes and myotube formation. Mechanistically, the binding of NDRG4 to carboxyl-terminal modulator protein (CTMP) abates the interaction of CTMP and protein kinase B (Akt) and increases the phosphorylation of Akt and cAMP response element binding protein (CREB), which leads to increased expression of myogenic genes. Our results reveal that NDRG4 promotes myogenic differentiation via Akt/CREB activation.
Keywords: Akt; CREB; CTMP; NDRG4; myogenesis.