Title | Caspase 3 cleavage of Pax7 inhibits self-renewal of satellite cells. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Dick SA, Chang NC, Dumont NA, Bell RAV, Putinski C, Kawabe Y, Litchfield DW, Rudnicki MA, Megeney LA |
Journal | Proc Natl Acad Sci U S A |
Volume | 112 |
Issue | 38 |
Pagination | E5246-52 |
Date Published | 2015 Sep 22 |
ISSN | 1091-6490 |
Keywords | Amino Acid Sequence, Animals, Binding Sites, Casein Kinases, Caspase 3, Cell Differentiation, Cell Lineage, Cells, Cultured, Immunohistochemistry, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Muscle, Skeletal, PAX7 Transcription Factor, Phosphorylation, Recombinant Proteins, Regeneration, Satellite Cells, Skeletal Muscle, Sequence Homology, Amino Acid, Stem Cells |
Abstract | Compensatory growth and regeneration of skeletal muscle is dependent on the resident stem cell population, satellite cells (SCs). Self-renewal and maintenance of the SC niche is coordinated by the paired-box transcription factor Pax7, and 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 SCs 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 SC self-renewal, whereas caspase activation leads to Pax7 cleavage and initiation of the myogenic differentiation program. Moreover, in vivo inhibition of caspase 3 activity leads to a profound disruption in skeletal muscle regeneration with an accumulation of SCs within the niche. We have also noted that casein kinase 2 (CK2)-directed phosphorylation of Pax7 attenuates caspase-directed cleavage. Together, these results demonstrate that SC fate is dependent on opposing posttranslational modifications of the Pax7 protein. |
DOI | 10.1073/pnas.1512869112 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 26372956 |
PubMed Central ID | PMC4586827 |
Grant List | / / Canadian Institutes of Health Research / Canada |
Submitted by kej2006 on June 6, 2018 - 4:11pm