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DOI | 10.1073/pnas.2021093118 |
Paxbp1 controls a key checkpoint for cell growth and survival during early activation of quiescent muscle satellite cells | |
Zhou S.; Han L.; Weng M.; Zhu H.; Heng Y.; Wang G.; Shen Z.; Chen X.; Fu X.; Zhang M.; Wu Z. | |
发表日期 | 2021 |
ISSN | 00278424 |
卷号 | 118期号:13 |
英文摘要 | Adult mouse muscle satellite cells (MuSCs) are quiescent in uninjured muscles. Upon muscle injury, MuSCs exit quiescence, reenter the cell cycle to proliferate and self-renew, and then differentiate and fuse to drive muscle regeneration. However, it remains poorly understood how MuSCs transition from quiescence to the cycling state. Here, we report that Pax3 and Pax7 binding protein 1 (Paxbp1) controls a key checkpoint during this critical transition. Deletion of Paxbp1 in adult MuSCs prevented them from reentering the cell cycle upon injury, resulting in a total regeneration failure. Mechanistically, we found an abnormal elevation of reactive oxygen species (ROS) in Paxbp1-null MuSCs, which induced p53 activation and impaired mTORC1 signaling, leading to defective cell growth, apoptosis, and failure in S-phase reentry. Deliberate ROS reduction partially rescued the cell-cycle reentry defect in mutant MuSCs. Our study reveals that Paxbp1 regulates a late cell-growth checkpoint essential for quiescent MuSCs to reenter the cell cycle upon activation. © 2021 National Academy of Sciences. All rights reserved. |
英文关键词 | Cell growth; Muscle satellite cells; Paxbp1; Quiescence; ROS |
语种 | 英语 |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/180060 |
作者单位 | State Key Laboratory of Molecular Neuroscience, Division of Life Science, Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong; Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen, 518055, China |
推荐引用方式 GB/T 7714 | Zhou S.,Han L.,Weng M.,et al. Paxbp1 controls a key checkpoint for cell growth and survival during early activation of quiescent muscle satellite cells[J],2021,118(13). |
APA | Zhou S..,Han L..,Weng M..,Zhu H..,Heng Y..,...&Wu Z..(2021).Paxbp1 controls a key checkpoint for cell growth and survival during early activation of quiescent muscle satellite cells.Proceedings of the National Academy of Sciences of the United States of America,118(13). |
MLA | Zhou S.,et al."Paxbp1 controls a key checkpoint for cell growth and survival during early activation of quiescent muscle satellite cells".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021). |
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