Caspase 3 Cleavage of Pax7 Inhibits Self-Renewal of Satellite Cells

Abstract

Compensatory growth and regeneration of skeletal muscle is dependent on the resident stem cell population, termed satellite cells. Self-renewal and maintenance of the satellite cell niche is coordinated by the transcription factor Pax7, yet continued expression of this protein inhibits the myoblast differentiation program. As such, the reduction or removal of Pax7 may denote a key prerequisite for satellite cells to abandon self-renewal and acquire differentiation competence. Here, we identify caspase 3 cleavage inactivation of Pax7 as a crucial step for terminating the self-renewal process. Inhibition of caspase 3 results in elevated Pax7 protein and satellite cell self-renewal, while caspase activation leads to Pax7 cleavage and initiation of the myogenic differentiation program. We have also noted that casein kinase 2 (CK2) directed phosphorylation of Pax7 attenuates caspase directed cleavage. Together, these results demonstrate that satellite cell fate is dependent on opposing post-translational modifications of the Pax7 protein.