The Ubiquitin-Proteasome System Is Indispensable for the Maintenance of Muscle Stem Cells

• DOI: 10.1016/j.stemcr.2018.10.009
• Publication Date: 2018-11-08T10:41:16Z
• Authors: Yasuo Kitajima; Naoki Suzuki; Aki Nunomiya; Shion Osana; Kiyoshi Yoshioka; Yoshitaka Tashiro; Ryosuke Takahashi; Yusuke Ono; Masashi Aoki; Ryoichi Nagatomi
• Keywords: p53; proteolysis; Medicine (General); Proteasome Endopeptidase Complex; muscle satellite cells; Satellite Cells, Skeletal Muscle; QH301-705.5; Apoptosis; Article; differentiation defect; Mice; 03 medical and health sciences; R5-920; proliferation defect; Animals; Regeneration; skeletal muscle; Biology (General); Muscle, Skeletal; Rpt3; Cells, Cultured; Cell Proliferation; Mice, Knockout; muscle regeneration; 0303 health sciences; Ubiquitin; Stem Cells; proteasome dysfunction; muscle stem cells; Phenotype; Tumor Suppressor Protein p53

Adult muscle stem cells (satellite cells) are required for adult skeletal regeneration. A proper balance between quiescence, proliferation, and differentiation is essential the maintenance of satellite cell pool their regenerative function. Although ubiquitin-proteasome most protein degradation in mammalian cells, how its dysfunction affects tissue remains unclear. Here, we investigated function proteasome using mice lacking crucial proteasomal component, Rpt3. Ablation Rpt3 decreased activity. Proteasome Rpt3-deficient impaired ability to proliferate, survive differentiate, resulting defective We found that inactivation activity induced proliferation defects apoptosis cells. Mechanistically, insufficient upregulated p53 pathway, which caused cell-cycle arrest. Our findings delineate a critical system maintaining muscle.