LAUSR

A large number of intracellular proteins are degraded by the ubiquitin-proteasome system, one of the major protein degradation pathways. It produces peptides of several different sizes through protein degradation, and these peptides are rapidly degraded into free amino acids by various intracellular aminopeptidases. Previously, we reported that the activity of proteasomes and aminopeptidases in the proteolysis pathway are necessary for myoblast proliferation and differentiation. However, the detailed function of intracellular aminopeptidases in myoblast proliferation and differentiation has not yet been elucidated. In this study, we focused on alanine aminopeptidase (APP) and investigated the function of APP in C2C12 myoblast proliferation and differentiation. In myoblasts and myotubes, APP was mainly localized in the cell membrane as well as expressed at low levels in the cytoplasm and nucleus. The reduction of the APP enzymatic activity impaired the cell cycle progression in C2C12 myoblasts. In addition, apoptosis was induced after APP-knockdown. Finally, myogenic differentiation was also delayed in the APP-suppressed myoblasts. These findings indicate that APP is required for myoblast proliferation and differentiation.