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

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2015 Sep 16

PMID 26372956

Citations 52

Authors

Sarah A Dick

Natasha C Chang

Nicolas A Dumont

Ryan A V Bell

Charis Putinski

Yoichi Kawabe

David W Litchfield

Michael A Rudnicki

Lynn A Megeney

Affiliations

Soon will be listed here.

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.

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