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DOI10.1073/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
ISSN00278424
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
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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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