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


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タイトル: The Ubiquitin-Proteasome System Is Indispensable for the Maintenance of Muscle Stem Cells
著者: Kitajima, Yasuo / Suzuki, Naoki / Nunomiya, Aki / Osana, Shion / Yoshioka, Kiyoshi / Tashiro, Yoshitaka / Takahashi, Ryosuke / Ono, Yusuke / Aoki, Masashi / Nagatomi, Ryoichi
発行日: 2018年12月11日
出版者: Cell Press
引用: Stem cell reports, 11(6), pp.1523-1538; 2018
抄録: Adult muscle stem cells (satellite cells) are required for adult skeletal muscle regeneration. A proper balance between quiescence, proliferation, and differentiation is essential for the maintenance of the satellite cell pool and their regenerative function. Although the ubiquitin-proteasome is required for most protein degradation in mammalian cells, how its dysfunction affects tissue stem cells remains unclear. Here, we investigated the function of the proteasome in satellite cells using mice lacking the crucial proteasomal component, Rpt3. Ablation of Rpt3 in satellite cells decreased proteasome activity. Proteasome dysfunction in Rpt3-deficient satellite cells impaired their ability to proliferate, survive and differentiate, resulting in defective muscle regeneration. We found that inactivation of proteasomal activity induced proliferation defects and apoptosis in satellite cells. Mechanistically, insufficient proteasomal activity upregulated the p53 pathway, which caused cell-cycle arrest. Our findings delineate a critical function of the proteasome system in maintaining satellite cells in adult muscle. It is not clear how proteasome insufficiency affects tissue stem cells. Kitajima et al. demonstrate that the proteasome system is indispensable for the maintenance of muscle stem cells. Proteasome dysfunction in Rpt3-deficient satellite cells impairs their ability to proliferate, survive and differentiate, resulting in defective muscle regeneration.
キーワード: differentiation defect / muscle regeneration / muscle satellite cells / muscle stem cells / p53 / proliferation defect / proteasome dysfunction / proteolysis / Rpt3 / skeletal muscle
URI: http://hdl.handle.net/10069/38771
ISSN: 22136711
DOI: 10.1016/j.stemcr.2018.10.009
権利: © 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:110 学術雑誌論文

引用URI : http://hdl.handle.net/10069/38771

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