杭州师范大学刘俊平研究团队发现,FBW7通过端粒脱帽来介导衰老和肺纤维化。这一研究成果于2020年10月20日在线发表在国际学术期刊《细胞—代谢》上。
Title: FBW7 Mediates Senescence and Pulmonary Fibrosis through Telomere Uncapping
Author: Lihui Wang, Ruping Chen, Guo Li, Zhiguo Wang, Jun Liu, Ying Liang, Jun-Ping Liu
Issue&Volume: 2020-10-21
Abstract: Tissue stem cells undergo premature senescence under stress, promoting age-relateddiseases; however, the associated mechanisms remain unclear. Here, we report thatin response to radiation, oxidative stress, or bleomycin, the E3 ubiquitin ligaseFBW7 mediates cell senescence and tissue fibrosis through telomere uncapping. FBW7binding to telomere protection protein 1 (TPP1) facilitates TPP1 multisite polyubiquitinationand accelerates degradation, triggering telomere uncapping and DNA damage response.Overexpressing TPP1 or inhibiting FBW7 by genetic ablation, epigenetic interference,or peptidomimetic telomere dysfunction inhibitor (TELODIN) reduces telomere uncappingand shortening, expanding the pulmonary alveolar AEC2 stem cell population in mice.TELODIN, synthesized from the seventh β strand blade of FBW7 WD40 propeller domain,increases TPP1 stability, lung respiratory function, and resistance to senescenceand fibrosis in animals chronically exposed to environmental stress. Our findingselucidate a pivotal mechanism underlying stress-induced pulmonary epithelial stemcell senescence and fibrosis, providing a framework for aging-related disorder interventions.
DOI: 10.1016/j.cmet.2020.10.004
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30537-4
Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
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